2,334 results on '"Triazolam"'
Search Results
2. Appropriate use of triazolam in elderly patients considering a quantitative benefit-risk assessment based on the pharmacokinetic-pharmacodynamic modeling and simulation approach supported by real-world data.
- Author
-
Okada, Akira, Sera, Shoji, and Nagai, Naomi
- Subjects
CONCOMITANT drugs ,OLDER patients ,OLDER people ,DRUG therapy ,CYTOCHROME P-450 - Abstract
Background: Triazolam is a typical drug commonly used in the elderly; however, there have been concerns about its adverse events resulting from age-related changes in physiological function and drug interactions with concomitant drugs. Thus, updated information contributing to the appropriate use based on the latest pharmacokinetic and post-marketing surveillance methods is needed. In this study, we evaluated the appropriate use of triazolam in the elderly by integrating real-world data with a modeling and simulation approach. Methods: The occurrence risk of adverse events in the elderly was evaluated using the spontaneous adverse event reporting regulatory databases from Japan and the United States. Information on drug concentrations and reactions was extracted from previous publications to estimate the threshold for plasma triazolam concentrations that cause adverse events. The pharmacokinetic/pharmacodynamic (PK/PD) model was then constructed, and the dose and administration were evaluated in various situations anticipated in medical practice. Results: Among all prescriptions, 25.4% were prescribed to individuals aged 80 years or above, and 51.8% were for those aged 70 years or above. A majority of cases involved CYP3A-metabolized drug combinations, accounting for 85.6%. Elderly individuals were at a higher risk of developing delirium and fall-fracture. Based on the constructed PK/PD model, the risk of adverse events increased when the plasma concentration of triazolam exceeded the calculated threshold of 0.44 ng/mL at approximately 6 h after administration. Administering 0.125 mg of triazolam, is half the approved dose for the elderly in Japan was deemed appropriate. Moreover, there was a substantial risk of adverse events even at a dosage of 0.0625 mg in combination with a moderate or strong inhibitor of cytochrome P450 3 A. Conclusion: Analyzing large-scale databases and existing research publications on PK/PD can practically contribute to optimizing triazolam drug therapy for the elderly in the daily clinical setting. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Long‐term benzodiazepine usage and mortality in patients with chronic non‐cancer musculoskeletal pain: A Nationwide cohort study.
- Author
-
Oh, Tak Kyu, Hwang, Insung, and Song, In‐Ae
- Subjects
- *
BENZODIAZEPINES , *RISK assessment , *NONSTEROIDAL anti-inflammatory agents , *STATISTICAL models , *SUBSTANCE abuse , *POST-traumatic stress disorder , *WOUNDS & injuries , *MUSCULOSKELETAL pain , *CHRONIC pain , *DIAZEPAM , *TRIAZOLAM , *T-test (Statistics) , *DISEASE duration , *STATISTICAL sampling , *CHLORDIAZEPOXIDE , *MULTIPLE regression analysis , *INSOMNIA , *MUSCULOSKELETAL system diseases , *QUESTIONNAIRES , *TRANQUILIZING drugs , *CAUSES of death , *DESCRIPTIVE statistics , *ALPRAZOLAM , *CHI-squared test , *AGE distribution , *SEVERITY of illness index , *RESPIRATORY diseases , *LONGITUDINAL method , *ODDS ratio , *NEUROLOGICAL disorders , *CHRONIC diseases , *ANALGESICS , *OPIOID analgesics , *GABAPENTIN , *DATA analysis software , *CLONAZEPAM , *SURVIVAL analysis (Biometry) , *CONFIDENCE intervals , *ANXIETY disorders , *COMORBIDITY , *PREGABALIN , *ACETAMINOPHEN , *PROPORTIONAL hazards models , *CLOBAZAM , *LORAZEPAM , *POISONING ,CARDIOVASCULAR disease related mortality - Abstract
Objectives: The impact of benzodiazepine use on mortality in patients with chronic non‐cancer pain (CNCP) has not been identified. We aimed to examine the factors associated with benzodiazepine use among patients with CNCP and examine whether long‐term benzodiazepine usage is associated with mortality in patients with CNCP. Methods: This study was conducted using data from the National Health Insurance Service database of South Korea. We selected 2.5% of all adult patients diagnosed with musculoskeletal diseases (MSD) in South Korea from 2010 to 2019 using a stratified random sampling technique and included them in the analysis as patients with CNCP. The risk of 10‐year all‐cause mortality in patients with CNCP was investigated using the 2010 cohort of patients with CNCP. Results: The proportion of the study population that used benzodiazepine during the 10‐year study period was 2.1% (390,683/18,770,234). Multivariable logistic regression showed that old age; increased Charlson comorbidity index (CCI); opioid, gabapentin or pregabalin, paracetamol, non‐steroidal anti‐inflammatory drugs, and Z‐drugs usage; and underlying psychiatric comorbidities were associated with increased benzodiazepine use. In addition, benzodiazepine use was associated with increased 10‐year all‐cause mortality (adjusted hazard ratio: 1.03, 95% confidence interval: 1.01, 1.06; p < 0.001). Conclusions: Benzodiazepine was prescribed to 2.1% of the patients with CNCP in South Korea from 2010 to 2019. Old age, increased CCI, underlying psychiatric comorbidities, and use of certain drugs are associated with increased use of benzodiazepines. In addition, benzodiazepine use is associated with 10‐year all‐cause mortality in patients with CNCP. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Triazolam for Pediatric Dental Sedation: A Retrospective Evaluation of Safety and Changes in Visit Behavior.
- Author
-
Yinger, Sheaffer, Claman, Daniel, Luca, Jennifer, Hammersmith, Kim, Gross, Erin, and Meyer, Beau
- Subjects
- *
MOLARS , *CHILD behavior , *DENTAL anesthesia , *OXYGEN saturation , *NONPARAMETRIC statistics , *HEART beat - Abstract
Purpose: To describe triazolam in pediatric dental mild to moderate sedation and report changes to overall visit behavior for permanent first molar extraction. Methods: This retrospective chart review from 2018 to 2022 analyzed demographic, procedural, and behavioral data for children eight years and older receiving triazolam for a permanent first molar extraction. The outcomes included adverse events measured by deviations in heart rate and oxygen saturation and changes to overall visit-level Frankl scores from the referral to sedation visit. Descriptive statistics and non-parametric statistical analyses were conducted. Results: The study population (n equals 82) was predominantly female (61 percent), English-speaking (85 percent), and White (41 percent) or Black (39 percent). The most common indication for mild to moderate sedation was dental anxiety (28 percent). There were zero instances of adverse events requiring emergency intervention or the use of reversal medication. The change in visit-level Frankl scores was significantly positive (P<0.001). Conclusion: Triazolam is likely a safe choice for mild to moderate sedation, leading to improved overall visit behavior in children undergoing a permanent first molar extraction. [ABSTRACT FROM AUTHOR]
- Published
- 2024
5. Next-Day Residual Effects of Gabapentin, Diphenhydramine and Triazolam on Simulated Driving Performance in Normal Volunteers
- Published
- 2021
6. Oral Sedation is Non-Inferior to Intravenous Sedation for Cornea and Glaucoma Surgery: A Randomized Controlled Trial
- Author
-
Lee HJ, Desai MA, Sadlak N, Fiorello MG, Githere WG, and Subramanian ML
- Subjects
triazolam ,midazolam ,oral sedation ,anesthesia ,cornea ,glaucoma ,ophthalmic surgery ,Ophthalmology ,RE1-994 - Abstract
Hyunjoo J Lee, Manishi A Desai, Natalie Sadlak, Marissa G Fiorello, Wanjiku G Githere, Manju L Subramanian, Department of Ophthalmology, Boston Medical Center, Boston, Massachusetts, USA, Department of Anesthesiology, Boston Medical Center, Boston, Massachusetts, USA, Department of Neurology, Boston Medical Center, Boston, Massachusetts, USA, Department of Investigational Pharmacy Services, Boston Medical Center, Boston, Massachusetts, USA, Noelle Crough Babak Eliassi-Rad Elizabeth S. Esparaz Jiwoo Kim Maria Velazquez-Lamela , MD Matthew Leidl Catherine V. Levitt Daniel J. Luther Heenal Marfatia Kambiz Negahban Steven Ness Crandall E. Peeler Tony Pira Rohini Rao Susannah Rowe Nicole H. Siegel Viha Vig, Wissam H. Mustafa Mark C. Norris Pavan Sekhar, Crandall E. Peeler, Stephen Zalewski On behalf of The Oral versus Intravenous Sedation Study GroupDepartment of Ophthalmology, Boston Medical Center, Boston, MA, USACorrespondence: Hyunjoo J Lee, Department of Ophthalmology, Boston Medical Center, 85 East Concord Street, 8th Floor, Boston, MA, 02118, USA, Tel +1 617 414 2020, Fax +1 617 414 2929, Email leehj@bu.eduPurpose: To determine whether oral sedation is as safe and effective as IV sedation for ophthalmic surgeries other than cataract surgery, we tested whether patient satisfaction with oral triazolam was non-inferior to IV midazolam for cornea and glaucoma surgeries.Patients and Methods: Seventy-five cornea and 49 glaucoma surgery patients 18 years and older at Boston Medical Center (Boston, MA) were randomized within each study group (cornea or glaucoma) to receive oral triazolam + IV placebo, or oral placebo + IV midazolam before surgery in a double-masked fashion. Supplemental IV anesthesia was administered as needed during surgery. The primary outcome measure was patient satisfaction with anesthesia, compared between oral and IV sedation groups via t-test for non-inferiority, based on 70 cornea and 43 glaucoma subjects completing the study. Secondary outcome measures included surgeon and anesthesia provider satisfaction with anesthesia, rate of supplemental IV anesthesia, and incidence of adverse events and surgical complications.Results: Using an a priori non-inferiority margin of 0.5, initial oral sedation was non-inferior to initial IV sedation in cornea (n=70, p< 0.001) and glaucoma (n=43, p=0.017) groups, even after excluding subjects administered supplemental IV anesthesia. There were no significant differences in anesthesia provider or surgeon satisfaction, intra-operative complications, adverse events, or supplemental anesthesia between groups, except for higher anesthesia provider satisfaction with oral sedation in an Ahmed or Baerveldt implant ± cataract surgery sub-group (p=0.04). Subjects receiving supplemental anesthesia included 6 oral (18.2%) and 5 IV (13.5%) in the cornea group (p=0.59), and 7 oral (29.2%) and 6 IV (31.6%) in the glaucoma group (p=0.50).Conclusion: Our results suggest that an initial dose of oral triazolam is equivalent to IV midazolam for non-cataract anterior segment surgeries. However, there was a relatively high need for supplemental IV anesthesia during some surgery types, particularly with glaucoma tube shunt implantation.Keywords: triazolam, midazolam, oral sedation, anesthesia, cornea, glaucoma, ophthalmic surgery
- Published
- 2022
7. Oral Versus Intravenous Sedation for Ocular Procedures
- Published
- 2020
8. Non-Steroidal Drug Interferences in a Quantitative Multisteroid LC-MS/MS Assay.
- Author
-
Braun, Valentin, Stuppner, Hermann, and Seger, Christoph
- Subjects
- *
LIQUID chromatography-mass spectrometry , *BENZODIAZEPINES , *MEDICAL screening , *QUALITY control , *PAROXETINE , *ISOTOPOLOGUES , *ANTIDEPRESSANTS - Abstract
Screening for possible interferences from steroidal compounds other than the target analytes (endogenous or exogenous) is well established in LC-MS/MS assay development for steroid quantification in a routine clinical setting. However, interferences from non-steroidal substances have, hitherto, not been explored. After screening more than 150 pharmaceuticals and their metabolites by analyzing commercial quality control samples from TDM analysis kits (Recipe, Chromsystems) with a multisteroid LC-MS/MS assay (protein precipitation followed by HybridSPE filtration, biphenyl column, methanol–water gradient with NH4F additive), we can report the finding of two newly discovered potential interferences from non-steroidal drugs. Antidepressant paroxetine (PX) was identified as an interference to 17-hydroxyprogesterone (17P), and α-hydroxytriazolam (α-OH-TZM)—a major metabolite of benzodiazepine triazolam (TZM)—was identified as an interference to aldosterone (ALDO). Despite different elemental and structural compositions and nominal masses, the M+1 isotopologues of PX and α-OH-TZM produced overlapping signals in ion traces monitored for the respective analytes (m/z 331 → 109/97 and 361→315/343, respectively). PX and TZM are frequently prescribed drugs, and their therapeutic ranges are far exceeding the reference ranges of 17P or ALDO (µmol vs nmol); therefore, these interferences should be considered clinically relevant. Striving for faster multi-analyte methods with high sample turnover, especially in the field of steroid quantification, can limit assay selectivity and specificity. Therefore, supported by the findings of this study, screening for potential interferences in multi-analyte LC-MS/MS method development should not cover only substances of the same class but also include a set of common drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
9. Comparison of Triazolam and Midazolam for Anxiolysis During Dental Treatment in the Pediatric Patient
- Author
-
Whitney Eichholz, Pediatric Dental Resident
- Published
- 2018
10. Pharmacovigilance in Gerontopsychiatric Patients (GAP)
- Published
- 2018
11. Oral Sedation
- Author
-
Haxhi, Christopher, Goupil, Michael T., Ferneini, Elie M., editor, and Goupil, Michael T., editor
- Published
- 2019
- Full Text
- View/download PDF
12. A Historical Overview of the Role of Benzodiazepines including Clonazepam in the Treatment of Adult Restless Legs Syndrome and Periodic Limb Movements in Sleep.
- Author
-
Walters AS, Spruyt K, Ba DM, and Gao X
- Subjects
- Humans, History, 20th Century, History, 21st Century, Adult, Restless Legs Syndrome drug therapy, Clonazepam therapeutic use, Benzodiazepines therapeutic use, Nocturnal Myoclonus Syndrome drug therapy
- Abstract
In a recent survey of 16,694 people receiving treatment for Restless Legs Syndrome (RLS), approximately 25% were treated with benzodiazepines either singly or in combination with other RLS treatments. Because of the large number of people receiving benzodiazepines for treatment of RLS, we conducted a historical overview of the therapeutic role of benzodiazepines in RLS and its associated condition Periodic Limb Movements in Sleep (PLMS). We found 17 articles on the use of clonazepam in RLS, PLMS, or both, 3 on triazolam and PLMS, 1 on alprazolam and RLS, 1 on temazepam and PLMS, and 1 on nitrazepam and PLMS. The order of benefit of benzodiazepines from the summarized literature is Sleep>RLS>PLMS and arousals > PLMS. Most of the studies on clonazepam employed dosages of 0.5-2.0 mg. Dosages of 3 or 4 mg caused lethargy, somnolence and confusion. An epidemiological study on the therapy of RLS suggests that treatment of RLS with most types of RLS medications including benzodiazepines in combination with other RLS therapies lowers the future cardiovascular risk associated with RLS. The major effect of benzodiazepines is through potentiation of the effect of GABA on the GABA A receptor. Neuroimaging studies suggest that GABA is altered either positively or negatively in various brain regions in RLS and genetic studies suggest that there are alterations in the GABA receptor in RLS. These results suggest that medications with different GABAergic mechanisms such as tiagabine (Gabitril) or others should be investigated in RLS for their possible therapeutic benefit., Highlights: Benzodiazepines are frequently used as therapy in Restless Legs Syndrome (RLS) and Periodic Limb Movements in Sleep. The order of benefit is Sleep>RLS>PLMS and arousals > PLMS. For clonazepam dosages of 0.5 mg-2.0 mg/day are most frequently employed. Benzodiazepines exert their therapeutic effect through GABA-ergic mechanisms., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
13. Effectiveness of GABA Agonists in Reducing the Reinforcing Effects of Cocaine
- Author
-
Craig R. Rush
- Published
- 2017
14. Sensitivity of Project: EVO Monitor Cognitive Measurements to Pharmacological Agents
- Published
- 2016
15. In vivo evaluation of intestinal human CYP3A inhibition by macrolide antibiotics in CYP3A-humanised mice.
- Author
-
Minegishi, Genki, Kazuki, Yasuhiro, Nitta, Shin-Ichiro, Miyajima, Atsushi, Akita, Hidetaka, and Kobayashi, Kaoru
- Subjects
- *
MACROLIDE antibiotics , *CLARITHROMYCIN , *INTESTINES , *DRUG interactions , *ARTIFICIAL chromosomes , *ERYTHROMYCIN , *CYTOCHROME P-450 CYP3A - Abstract
It is important to predict drug-drug interactions via inhibition of intestinal cytochrome P450 3A (CYP3A) which is a determinant of bioavailability of orally administered CYP3A substrates. However, inhibitory effects of macrolide antibiotics on CYP3A-mediated metabolism are not entirely identical between humans and rodents. We investigated the effects of macrolide antibiotics, clarithromycin and erythromycin, on in vitro and in vivo metabolism of triazolam, a CYP3A substrate, in CYP3A-humanised mice generated by using a mouse artificial chromosome vector carrying a human CYP3A gene. Metabolic activities of triazolam were inhibited by macrolide antibiotics in liver and intestine microsomes of CYP3A-humanised mice. The area under the plasma concentration-time curve ratios of 4-hydroxytriazolam to triazolam after oral dosing of triazolam were significantly decreased by multiple administration of macrolide antibiotics. The plasma concentrations ratios of α-hydroxytriazolam and 4-hydroxytriazolam to triazolam in portal blood were significantly decreased by multiple administration of clarithromycin in CYP3A-humanised mice. These results suggest that intestinal CYP3A activity was inhibited by macrolide antibiotics in CYP3A-humanised mice in vitro and in vivo. The plasma concentrations of triazolam and its metabolites in the portal blood of CYP3A-humanised mice would be useful for direct evaluation of intestinal CYP3A-mediated drug-drug interactions. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
16. A Study to Determine Whether an Oral Drops Formulation of Triazolam is Bioequivalent to a Tablet Formulation in Healthy Subjects
- Published
- 2016
17. Triazolam Trial In Healthy Subjects To Compare Bioavailability Between Formulations Of Triazolam To Determine Their Bioequivalence In Terms Of Rate And Magnitude Of Absorption
- Author
-
Investigación Farmacológica y Biofarmacéutica and Director, Clinical Trial Disclosure Group
- Published
- 2016
18. Treatment Failure and Long-Term Prescription Risk for Guideline-Recommended Hypnotics in Japan.
- Author
-
Takeshima M, Yoshizawa K, Ogasawara M, Kudo M, Itoh Y, Ayabe N, and Mishima K
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Cohort Studies, Eszopiclone, Hypnotics and Sedatives adverse effects, Japan, Retrospective Studies, Treatment Failure, Zolpidem adverse effects, Indenes, Sleep Initiation and Maintenance Disorders drug therapy, Triazolam
- Abstract
Importance: Although insomnia guidelines recommend the use of several individual hypnotics, the most useful hypnotic for treating insomnia in a clinical setting remains unclear., Objective: To determine which guideline-recommended hypnotics have lower risks of monotherapy failure and which hypnotics have a higher risk of long-term prescription for insomnia treatment., Design, Setting, and Participants: This retrospective observational cohort study used data from the Japan Medical Data Center Claims Database from April 1, 2005, to March 31, 2021. Participants included adults whose first prescribed pharmaceutical treatment for insomnia was guideline-recommended hypnotic monotherapy. Data were analyzed from December 24, 2022, to September 26, 2023., Exposures: Suvorexant, ramelteon, eszopiclone, zolpidem, and triazolam monotherapy., Main Outcomes and Measures: The primary outcome was monotherapy failure, defined as a change in hypnotic or having an additional hypnotic prescribed for insomnia within 6 months of the first prescription of a guideline-recommended hypnotic monotherapy. The secondary outcome was monotherapy discontinuation, defined as no prescription of any hypnotic for 2 consecutive months within 6 months after prescribing a guideline-recommended hypnotic in patients for whom monotherapy did not fail. Monotherapy failure and discontinuation were compared using Cox proportional hazards and logistic regression models, respectively., Results: The study included 239 568 adults (median age, 45 [IQR, 34-55] years; 50.2% women) whose first prescription for insomnia was guideline-recommended hypnotic monotherapy. During the 6-month follow-up period, 24 778 patients (10.3%) experienced failure of monotherapy with a guideline-recommended hypnotic. In comparison with eszopiclone, there were more cases of monotherapy failure for ramelteon (adjusted hazard ratio [AHR], 1.23 [95% CI], 1.17-1.30; P < .001), fewer cases for zolpidem (AHR, 0.84 [95% CI, 0.81-0.87]; P < .001) and triazolam (AHR, 0.82 [95% CI, 0.78-0.87]; P < .001), and no significant difference between suvorexant and eszopiclone. Among those without monotherapy failure, monotherapy was discontinued in 84.6% of patients, with more discontinuations for ramelteon (adjusted odds ratio [AOR], 1.31 [95% CI, 1.24-1.40]; P < .001) and suvorexant (AOR, 1.20 [95% CI, 1.15-1.26]; P < .001) than for eszopiclone and no significant difference between zolpidem or triazolam and eszopiclone., Conclusions and Relevance: Due to uncontrolled confounding factors in this cohort study, no conclusions regarding the pharmacologic properties of guideline-recommended hypnotics can be drawn based on these results. Further studies accounting for confounding factors, including diagnoses of chronic vs acute insomnia disorder, insomnia and psychiatric symptom severity, and physician attitudes toward hypnotic prescription, are needed.
- Published
- 2024
- Full Text
- View/download PDF
19. Dependence liability of lormetazepam: are all benzodiazepines equal? The case of the new i.v. lormetazepam for anesthetic procedures.
- Author
-
Horowski, Reinhard
- Subjects
- *
OPERATIVE surgery , *ANXIETY treatment , *FLUMAZENIL , *PROPOFOL infusion syndrome , *BENZODIAZEPINES , *PREMEDICATION , *ANESTHESIOLOGISTS , *PREANESTHETIC medication - Abstract
There are contradictory publications and reports regarding the dependence liability of the 3-hydroxy-benzo-1,4-diazepine derivative lormetazepam, one of the most often prescribed hypnotic benzodiazepines which is now also available as an intravenous (i.v.) product for anesthetists. The author was involved in the preclinical and subsequently in the clinical development and post-marketing surveillance of lormetazepam. Here, he reviews the published and unpublished data about lormetazepam dependence and proposes explanations for contradictory views from other authors. On this basis and in contrast to class labeling from regulatory bodies and WHO, the author comes to the conclusion that use of lormetazepam definitely carries a lower risk of inducing dependence and causing abuse than most other benzodiazepines. This applies as well to Sedalam®, the new i.v. application form of lormetazepam, which is much better tolerated than propofol. Because of its pharmacokinetic properties and because all its effects can be fully antagonized with the benzodiazepine antagonist flumazenil, this innovative intravenous application form of lormetazepam provides an excellent method for premedication, symptomatic treatment of excitation and anxiety in the context of surgical or diagnostic procedures including outpatient interventions and for basic sedation during anesthesia. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
20. Comparison of the hepatic metabolism of triazolam in wild-type andCyp3a-knockout mice for understanding CYP3A-mediated metabolism inCYP3A-humanised mice in vivo.
- Author
-
Minegishi, Genki, Kazuki, Yasuhiro, Yamasaki, Yuki, Okuya, Fuka, Akita, Hidetaka, Oshimura, Mitsuo, and Kobayashi, Kaoru
- Subjects
- *
KNOCKOUT mice , *MICE , *CYTOCHROME P-450 , *INTRAVENOUS therapy , *METABOLISM , *PREGNENOLONE - Abstract
1. To investigate cytochrome P450 3A (CYP3A)-mediated metabolism in vivo, plasma concentrations of triazolam (TRZ) are often monitored as a CYP3A marker in CYP3A-humanised mice. However, it has not been determined whether plasma concentrations of TRZ after intravenous administration can reflect hepatic CYP3A activity in CYP3A-humanised mice. 2. Firstly, we investigated the pharmacokinetics of TRZ in wild-type and Cyp3a-knockout (Cyp3a-KO) mice. Plasma concentration profiles of TRZ and α-hydroxy (OH) TRZ were very similar in wild-type and Cyp3a-KO mice. On the other hand, AUC of 4-OH TRZ in Cyp3a-KO mice was significantly lower than that in wild-type mice. Pregnenolone 16α-carbonitrile (PCN) decreased the areas under the plasma concentration-time curves (AUCs) of TRZ and α-OH TRZ in both groups. There was no significant effect of PCN on AUC of 4-OH TRZ in Cyp3a-KO mice. 3. Next, we verified that AUC of 4-OH TRZ in CYP3A-humanised mice was higher than that in Cyp3a-KO mice, although the difference was not significant. 4. In conclusion, plasma concentrations of 4-OH TRZ, but not those of TRZ and α-OH TRZ, might reflect hepatic CYP3A activity in mice in vivo. These results provide important insights for in vivo studies using a CYP3A-humanised model. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
21. A Study to Evaluate the Clinical Efficacy, Safety and Tolerability of ARX-F03 Sublingual Sufentanil/Triazolam NanoTab™ in Patients Undergoing an Elective Abdominal Liposuction Procedure
- Published
- 2014
22. When Enough Is Now Too Much : Fatal Forty DDI: midazolam, itraconazole, CYP3A4
- Author
-
Wittwer, Erica D., Sprung, Juraj, Nicholson, Wayne T., Marcucci, Catherine, editor, Hutchens, Michael P., editor, Wittwer, Erica D., editor, Weingarten, Toby N., editor, Sprung, Juraj, editor, Nicholson, Wayne T., editor, Lalwani, Kirk, editor, Metro, David G., editor, Dull, Randal O., editor, Swide, Christopher E., editor, Seagull, F. Jacob, editor, Kirsch, Jeffrey R., editor, and Sandson, Neil B., editor
- Published
- 2015
- Full Text
- View/download PDF
23. A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasally Administered Esketamine in Healthy Participants
- Published
- 2013
24. Zydus receives USFDA approval for Triazolam tablets
- Subjects
United States. Food and Drug Administration ,Drug approval ,Triazolam ,News, opinion and commentary - Abstract
Zydus Lifesciences has received final approval from the United States Food and Drug Administration (USFDA) to market Triazolam Tablets USP, 0.125 mg and 0.25 mg (USRLD: HALCIONaà tablets). Triazolam tablets [...]
- Published
- 2023
25. The effect of triazolam premedication on anxiety, sedation, and amnesia in general anesthesia
- Author
-
Taehee Pyeon, Shiyoung Chung, Injae Kim, Seongheon Lee, and Seongwook Jeong
- Subjects
amnesia ,anxiety ,benzodiazepines ,premedication ,triazolam ,Anesthesiology ,RD78.3-87.3 - Abstract
BackgroundBenzodiazepines have been used preoperatively as part of an anesthesia regimen to attenuate the anxiety of patients. In this study, we aimed to examine the effect of oral triazolam, a short-acting benzodiazepine, on anxiety, sedation, and amnesia.MethodsNinety patients, aged 20–55 years, were randomly assigned to receive no premedication, or to receive triazolam 0.25 mg or 0.375 mg 1 h before anesthesia. Anxiety score, sedation score, blood pressure, heart rate and psychomotor performance were measured on the evening before surgery and on the day of surgery. Additional tests of psychomotor performance were performed in the postanesthesia care unit and on the next day of surgery. The occurrence of amnesia, bispectral index (BIS), recovery profiles and patient satisfaction with overall anesthesia care were also evaluated.ResultsChanges in the anxiety and sedation scores on the day of surgery were not significantly different among groups, whereas the increases in systolic blood pressure and heart rate were significantly less in both triazolam groups. The triazolam groups both showed a higher incidence of high satisfaction scores (≥ 2). The two triazolam groups also showed similar outcomes, except for a dose-dependent increase in the number of patients with amnesia and BIS values < 90. Delayed recovery from general anesthesia and psychomotor impairment were not observed in the triazolam groups.ConclusionsTriazolam 0.25 mg or 0.375 mg reduced the hemodynamic changes associated with anxiety, produced potent amnesia, and improved patient satisfaction. We suggest that triazolam can be used effectively as anesthetic premedication in adults.
- Published
- 2017
- Full Text
- View/download PDF
26. Behavioral and Subjective Efficacy of Ramelteon in Subjects With a History of Polydrug Abuse
- Published
- 2012
27. Orexin Receptor Blockade-Induced Sleep Preserves the Ability to Wake in the Presence of Threat in Mice
- Author
-
Shouhei Iwakawa, Yuichi Kanmura, and Tomoyuki Kuwaki
- Subjects
orexin ,hypocretin ,hypnotics ,dual orexin receptor antagonist ,triazolam ,aversive stimuli ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Retention of the ability to wake from sleep in response to dangerous situations is an ideal characteristic of safe hypnotics. We studied the effects of a dual orexin receptor antagonist-22 (DORA-22) and the GABA-A receptor modulator, triazolam, on the ability to wake in response to aversive stimuli. We examined four modalities of sensory inputs, namely, auditory (ultrasonic sound), vestibular (trembling), olfactory (predator odor), and autonomic (hypoxia) stimuli. When the mice fell asleep, one of the four stimuli was applied for 30 s. In the case of auditory stimulation, latency to arousal following vehicle, DORA-22, and triazolam administration was 3.0 (2.0–3.8), 3.5 (2.0–6.5), and 161 (117–267) s (median and 25–75 percentile in the parentheses, n = 8), respectively. Latency to return to sleep after arousal was 148 (95–183), 70 (43–98), and 60 (52–69) s, respectively. Similar results were obtained for vestibular and olfactory stimulation. During the hypoxic stimulation, latencies for arousal and returning to sleep were not significantly different among the groups. The findings of this study are consistent with the distinct mechanisms of these sleep promoting therapies; GABA-A receptor activation by triazolam is thought to induce widespread central nervous system (CNS) suppression while DORA-22 more specifically targets sleep/wake pathways through orexin receptor antagonism. These data support the notion that DORA-22 preserves the ability to wake in response to aversive and consciousness-inducing sensory stimuli, regardless of modality, while remaining effective in the absence of threat. This study provides a unique and important safety evaluation of the potential for certain hypnotics.
- Published
- 2019
- Full Text
- View/download PDF
28. Inhibitory Actions of Antidepressants, Hypnotics, and Anxiolytics on Recombinant Human Acetylcholinesterase Activity.
- Author
-
Obara K, Mori H, Ihara S, Yoshioka K, and Tanaka Y
- Subjects
- Humans, Acetylcholinesterase, Hypnotics and Sedatives pharmacology, Hypnotics and Sedatives therapeutic use, Sertraline, Clomipramine, Mirtazapine, Paroxetine, Citalopram, Escitalopram, Buspirone, Antidepressive Agents pharmacology, Antidepressive Agents therapeutic use, Anti-Anxiety Agents pharmacology, Anti-Anxiety Agents therapeutic use, Amoxapine, Triazolam
- Abstract
Alzheimer's disease (AD) is accompanied by behavioral and psychological symptoms of dementia (BPSD), which is often alleviated by treatment with psychotropic drugs, such as antidepressants, hypnotics, and anxiolytics. If these drugs also inhibit acetylcholinesterase (AChE) activity, they may contribute to the suppression of AD progression by increasing brain acetylcholine concentrations. We tested the potential inhibitory effects of 31 antidepressants, 21 hypnotics, and 12 anxiolytics on recombinant human AChE (rhAChE) activity. At a concentration of 10
-4 M, 22 antidepressants, 19 hypnotics, and 11 anxiolytics inhibited rhAChE activity by <20%, whereas nine antidepressants (clomipramine, amoxapine, setiptiline, nefazodone, paroxetine, sertraline, citalopram, escitalopram, and mirtazapine), two hypnotics (triazolam and brotizolam), and one anxiolytic (buspirone) inhibited rhAChE activity by ≥20%. Brotizolam (≥10-6 M) exhibited stronger inhibition of rhAChE activity than the other drugs, with its pIC50 value being 4.57 ± 0.02. The pIC50 values of the other drugs were <4, and they showed inhibitory activities toward rhAChE at the following concentrations: ≥3 × 10-6 M (sertraline and buspirone), ≥10-5 M (amoxapine, nefazodone, paroxetine, citalopram, escitalopram, mirtazapine, and triazolam), and ≥3 × 10-5 M (clomipramine and setiptiline). Among these drugs, only nefazodone inhibited rhAChE activity within the blood concentration range achievable at clinical doses. Therefore, nefazodone may not only improve the depressive symptoms of BPSD through its antidepressant actions but also slow the progression of cognitive symptoms of AD through its AChE inhibitory actions.- Published
- 2024
- Full Text
- View/download PDF
29. Effect of pretreatment regimens of 1-aminobenzotriazole on metabolism and gastric emptying of probe compounds in rat.
- Author
-
Padmanabhan, Shweta, Kaur, Harbeer, Rao, Abhijith, Mariappan, T. Thanga, Holenarsipur, Vinay K., Saxena, Ajay, and Gupta, Yogesh Kumar
- Subjects
- *
ENZYME inhibitors , *TRIAZOLAM , *ACETAMINOPHEN , *GASTRIC emptying , *METABOLISM , *PHARMACOKINETICS - Abstract
1-Aminobenzotriazole (ABT) is a mechanism-based inactivator of major cytochrome P450 (CYP) enzymes, which is used in multiple mechanistic studies. The purpose was to evaluate the effect of 2 and 16-h pretreatment regimens of ABT on the exposures of triazolam in rat. Another objective was to evaluate the effect of ABT on gastric emptying of acetaminophen. Plasma area under the curve (AUC) of triazolam was increased by 101-fold and 81-fold for the rats pretreated with ABT at 2 and 16 h, respectively, compared to control rats. Time to reach maximum concentration was 0.3, 4.8 and 3.7 h in control, 2 and 16-h pretreatment animals, respectively. In the case of acetaminophen, where Tmax was not delayed, the mean absorption time (MAT) in control, 2 and 16 h ABT pretreatment groups were 0.3, 4.6 and 2.9 h, respectively, suggesting delayed absorption. This hypothesis was further supported by GastroPlusTM simulation. In summary, extent of triazolam absorption was increased to a similar extent with both 2 and 16 h ABT pretreatment regimens, suggesting that either of the regimen can be used to increase parent exposures in rat. With ABT pretreatment, delayed absorption of triazolam and acetaminophen was observed, as suggested by delay in Tmax and MAT, respectively. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
30. GABAA Receptor Subtypes and the Abuse‐Related Effects of Ethanol in Rhesus Monkeys: Experiments with Selective Positive Allosteric Modulators.
- Author
-
Berro, Lais F., Rüedi‐Bettschen, Daniela, Cook, Jemma E., Golani, Lalit K., Li, Guanguan, Jahan, Rajwana, Rashid, Farjana, Cook, James M., Rowlett, James K., and Platt, Donna M.
- Subjects
- *
ALCOHOLISM , *ALCOHOLS (Chemical class) , *ANIMAL experimentation , *CELL receptors , *ETHANOL , *FOOD service , *ORAL drug administration , *PRIMATES , *SELF medication , *SUCROSE , *ZOLPIDEM , *TRIAZOLAM - Abstract
Background: Previous studies have investigated α1GABAA and α5GABAA receptor mechanisms in the behavioral effects of ethanol (EtOH) in monkeys. However, genetic studies in humans and preclinical studies with mutant mice suggest a role for α2GABAA and/or α3GABAA receptors in the effects of EtOH. The development of novel positive allosteric modulators (PAMs) with functional selectivity (i.e., selective efficacy) at α2GABAA and α3GABAA receptors allows for probing of these subtypes in preclinical models of the discriminative stimulus and reinforcing effects of EtOH in rhesus macaques. Methods: In discrimination studies, subjects were trained to discriminate EtOH (2 g/kg, intragastrically) from water under a fixed‐ratio (FR) schedule of food delivery. In oral self‐administration studies, subjects were trained to self‐administer EtOH (2% w/v) or sucrose (0.3 to 1% w/v) under an FR schedule of solution availability. Results: In discrimination studies, functionally selective PAMs at α2GABAA and α3GABAA (HZ‐166) or α3GABAA (YT‐III‐31) receptors substituted fully (maximum percentage of EtOH‐lever responding ≥80%) for the discriminative stimulus effects of EtOH without altering response rates. Full substitution for EtOH also was engendered by a nonselective PAM (triazolam), an α5GABAA‐preferring PAM (QH‐ii‐066) and a PAM at α2GABAA, α3GABAA, and α5GABAA receptors (L‐838417). A partial (MRK‐696) or an α1GABAA‐preferring (zolpidem) PAM only engendered partial substitution (i.e., ~50 to 60% EtOH‐lever responding). In self‐administration studies, pretreatments with the functionally selective PAMs at α2GABAA and α3GABAA (XHe‐II‐053 and HZ‐166) or α3GABAA (YT‐III‐31 and YT‐III‐271) receptors increased EtOH, but not sucrose, drinking at doses that had few, or no, observable sedative‐motor effects. Conclusions: Our results confirm prior findings regarding the respective roles of α1GABAA and α5GABAA receptors in the discriminative stimulus effects of EtOH and, further, suggest a key facilitatory role for α3GABAA and potentially α2GABAA receptors in several abuse‐related effects of EtOH in monkeys. Moreover, they reveal a potential role for these latter subtypes in EtOH's sedative effects. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
31. Reevaluate In Vitro CYP3A Index Reactions of Benzodiazepines and Steroids between Humans and Dogs
- Author
-
QingLiang, Wu, YiTing, Hu, CuiTong, Wang, Wei, Wei, LanLan, Gui, WuShuang, Zeng, Changxiao, Liu, Wei, Jia, Jia, Miao, and Ke, Lan
- Subjects
Pharmacology ,Alprazolam ,Midazolam ,Pharmaceutical Science ,Triazolam ,Hydroxylation ,Benzodiazepines ,Kinetics ,Dogs ,Species Specificity ,Microsomes, Liver ,Animals ,Cytochrome P-450 CYP3A ,Humans ,Protein Isoforms ,Steroids ,Deoxycholic Acid - Abstract
Cytochrome P450 3A (CYP3A), the most important class of drug-metabolizing enzymes, participates in the metabolism of half of clinically used drugs. The CYP3A index reactions of dogs, one of the most widely used preclinical nonrodent species, are still poorly understood. This work evaluated the activity and selectivity of 10 CYP3A index reactions, including midazolam (MDZ) 1'- and 4-hydroxylation, alprazolam (APZ) and triazolam (TRZ)
- Published
- 2022
32. Past-year use or misuse of an opioid is associated with use of a sedative-hypnotic medication: a US National Survey on Drug Use and Health (NSDUH) study
- Author
-
Michael A. Grandner, Sadia Ghani, Michael D. Stein, Michelle Naps, Subhajit Chakravorty, and Andrew S. Tubbs
- Subjects
Pulmonary and Respiratory Medicine ,Benzodiazepine ,medicine.medical_specialty ,Triazolam ,Eszopiclone ,Temazepam ,medicine.drug_class ,business.industry ,Opioid-Related Disorders ,Scientific Investigations ,Health Surveys ,Analgesics, Opioid ,Benzodiazepines ,Zaleplon ,Neurology ,Opioid ,Sedative ,Sedative/hypnotic ,medicine ,Humans ,Hypnotics and Sedatives ,Neurology (clinical) ,Psychiatry ,business ,medicine.drug - Abstract
STUDY OBJECTIVES: Prescription use and misuse of opioids are linked to greater sleep disturbance. However, there are limited data on the prevalence of sedative-hypnotic medication use among persons who use opioids. Therefore, this study examined whether past-year sedative-hypnotic use among persons who used/misused opioids was higher than among individuals who did not use opioids. METHODS: Data were acquired from the US National Survey on Drug Use and Health for 2015–2018. Use of a sedative benzodiazepine (temazepam, flurazepam, triazolam) or a Z-drug (eszopiclone, zaleplon, zolpidem) was examined in relation to use/misuse of an opioid within the past year. Logistic regression models estimated the associations between opioids and sedative-hypnotics using inverse probability of treatment weighting. A secondary machine learning analysis tested 6 binary classifiers to predict sedative-hypnotic use based on opioid use/misuse and other covariates. RESULTS: Of 171,766 respondents, 24% used a prescription opioid whereas 3.6% misused an opioid in the past year. Among those who used a prescription opioid, 1.9% received a sedative benzodiazepine and 9% received a Z-drug during the same time frame. Use of an opioid was associated with greater odds of sedative benzodiazepine use (odds ratio, 4.4; 95% confidence interval, 3.61–5.4) and Z-drug use (odds ratio, 3.8; 95% confidence interval, 3.51–4.09), and stronger associations were noted for misuse of an opioid. Machine learning models accurately classified sedative-hypnotic medication use for > 70% of respondents based on opioid use/misuse. CONCLUSIONS: Sedative-hypnotic use is common among persons who use opioids, which is of concern given the elevated mortality risk with concurrent use of these substances. CITATION: Tubbs AS, Ghani SB, Naps M, Grandner MA, Stein MD, Chakravorty S. Past-year use or misuse of an opiod is associated with use of a sedative-hypnotic medication: a US National Survey on Drug Use and Health (NSDUH) study. J Clin Sleep Med. 2022;18(3):809–816.
- Published
- 2022
33. Effects of zolpidem/triazolam on cognitive performance 12 hours after acute administration.
- Author
-
Matsunaga, Yusuke, Tagaya, Hirokuni, Fukase, Yuko, Hakamata, Yuko, Murayama, Norio, Kumagai, Yuji, and Kuroyama, Masakazu
- Subjects
- *
ZOLPIDEM , *COGNITIVE ability , *DRUG administration , *HYPNOTICS , *POLYSOMNOGRAPHY - Abstract
Objective: Most previous studies have concluded that decreased cognitive function and performance due to ultra-short acting hypnotics do not persist after 6-9 h post-administration. This study examined the effects of ultra-short acting hypnotics on cognitive function and performance 12 h after administration, ie, a time considered sufficient for the effects of hypnotics to disappear.Methods: Thirteen healthy young male volunteers (mean age, 23.4 ± 3.2 years) participated in this study. Participants attended three sessions of polysomnography (PSG) recording preceded by oral administration of placebo for the first session, and 5 mg zolpidem or 0.25 mg triazolam for the second and third sessions, in a double-blinded, randomized manner at intervals of at least five days. A cognitive test battery was administered following each session, consisting of a psychomotor vigilance task (PVT), which reflects alertness and sleepiness, digit symbol substitution test (DSST), which reflects attention and working memory function, and assessment of subjective sleepiness and mental condition using a visual analog scale (VAS).Results and Conclusions: The administration of hypnotics significantly increased total sleep time, sleep efficiency, and sleep stages 2 and 4, and significantly decreased wake after sleep onset and sleep stage 1. PVT parameters were not affected by the administration of hypnotics, but DSST score was significantly lower, and "subjective alertness," "vigor," and "sadness" significantly deteriorated, after administration. In conclusion, while objective sleepiness disappeared 12 h after the administration of ultra-short acting hypnotics, their effects to decrease cognitive function persisted even after 12 h post-administration. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
34. Triazolam Improves Sleep but Fails to Alter Pain in TMD Patients.
- Author
-
DeNucci, Donald J., Sobiski, Christine, and Dionne, Raymond A.
- Subjects
TRIAZOLAM ,OROFACIAL pain ,TEMPOROMANDIBULAR disorders ,MASTICATORY muscles ,PLACEBOS ,SLEEP stages ,SLEEP disorders ,PALPATION ,ELECTROMYOGRAPHY - Abstract
Copyright of Journal of Orofacial Pain is the property of Quintessence Publishing Company Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 1998
35. Triazolam
- Author
-
Akins, Cristy, Gonzalez, Efrain Antonio, Kreutzer, Jeffrey S., editor, DeLuca, John, editor, and Caplan, Bruce, editor
- Published
- 2018
- Full Text
- View/download PDF
36. Physiological, Behavioral and Subjective Effects of Drugs (GHB)
- Author
-
Johns Hopkins University and Senior Director of Clinical Development
- Published
- 2008
37. Tropical Punch Packing a Real Knockout : Fatal Forty DDI: grapefruit juice, midazolam, CYP3A4
- Author
-
Blasiole, Brian, Beaman, Shawn T., Marcucci, Catherine, editor, Hutchens, Michael P., editor, Wittwer, Erica D., editor, Weingarten, Toby N., editor, Sprung, Juraj, editor, Nicholson, Wayne T., editor, Lalwani, Kirk, editor, Metro, David G., editor, Dull, Randal O., editor, Swide, Christopher E., editor, Seagull, F. Jacob, editor, Kirsch, Jeffrey R., editor, and Sandson, Neil B., editor
- Published
- 2015
- Full Text
- View/download PDF
38. A Study of Islanders that Examines the Effect of Age on the Impact of anti-anxiety medicine on memory recall?
- Author
-
Hongxu Zha
- Subjects
Psychiatry ,alprazolam ,Medicine and Health Sciences ,Medical Specialties ,anti-anxiety medicine ,memory recall ,triazolam - Abstract
This research aimed to investigate how age differentiate the impact of anti-anxiety medicine, namely alprazolam and triazolam on memory recall, using the islander dataset from Kaggle.
- Published
- 2023
- Full Text
- View/download PDF
39. Investigation on toxicological usefulness of synovial fluids, as an alternative matrix: postmortem distribution/redistribution of triazolam and its predominant metabolite α-hydroxytriazolam in human body fluids
- Author
-
Naotomo Miyoshi, Hideki Nozawa, Koutaro Hasegawa, Kayoko Minakata, Itaru Yamagishi, Amin Wurita, and Masako Suzuki
- Subjects
Chromatography ,Triazolam ,Chemistry ,Metabolite ,Biochemistry (medical) ,Pharmacology toxicology ,Toxicology ,Body Fluids ,Pathology and Forensic Medicine ,Matrix (chemical analysis) ,Feces ,chemistry.chemical_compound ,Synovial Fluid ,medicine ,Humans ,Distribution (pharmacology) ,Hydroxytriazolam ,Redistribution (chemistry) ,medicine.drug - Published
- 2021
40. Zydus Lifesciences gets final approval from USFDA for Triazolam Tablets
- Subjects
United States. Food and Drug Administration ,Drug approval ,Triazolam ,Business, international - Abstract
The drug will be manufactured at the group's formulation manufacturing facility at Moraiya, Ahmedabad, India Zydus Lifesciences has received final approval from the United States Food and Drug Administration (USFDA) [...]
- Published
- 2022
41. PBPK Analysis to Study the Impact of Genetic Polymorphism of NAT2 on Drug-Drug Interaction Potential of Isoniazid
- Author
-
Saranjit Singh and Ankit Balhara
- Subjects
Adult ,Male ,Phenytoin ,Triazolam ,Genotype ,Arylamine N-Acetyltransferase ,Antitubercular Agents ,Pharmaceutical Science ,CYP2C19 ,Pharmacology ,Polymorphism (computer science) ,Isoniazid ,medicine ,Cytochrome P-450 CYP3A ,Humans ,Tuberculosis ,Drug Interactions ,heterocyclic compounds ,Pharmacology (medical) ,Prospective Studies ,Aged ,Polymorphism, Genetic ,CYP3A4 ,business.industry ,Organic Chemistry ,Acetylation ,Middle Aged ,bacterial infections and mycoses ,Cytochrome P-450 CYP2C19 ,Molecular Medicine ,Female ,business ,Diazepam ,Rifampicin ,Biotechnology ,medicine.drug - Abstract
Isoniazid (INH) is prescribed both for the prophylaxis as well as the treatment of tuberculosis. It is primarily metabolized through acetylation by a highly polymorphic enzyme, N-acetyl transferase 2 (NAT2), owing to which significant variable systemic drug levels have been reported among slow and rapid acetylators. Furthermore, many drugs, like phenytoin, diazepam, triazolam, etc., are known to show toxic manifestation when co-administered with INH and it happens prominently among slow acetylators. Additionally, it is revealed in in vitro inhibition studies that INH carries noteworthy potential to inhibit CYP2C19 and CYP3A4 enzymes. However, CYP inhibitory effect of INH gets masked by opposite enzyme-inducing effect of rifampicin, when used in combination. Thus, distinct objective of this study was to fill the knowledge gaps related to gene-drug-drug interactions (DDI) potential of INH when given alone for prophylactic purpose. Whole body-PBPK models of INH were developed and verified for both slow and fast acetylators. The same were then utilized to carry out prospective DDI studies with CYP2C19 and CYP3A4 substrates in both acetylator types. The results highlighted likelihood of significant higher blood levels of CYP2C19 and CYP3A4 substrate drugs in subjects receiving INH pre-treatment. It was also re-established that interaction was more likely in slow acetylators, as compared to rapid acetylators. The novel outcome of the present study is the indication that prescribers should give careful consideration while advising CYP2C19 and CYP3A4 substrate drugs to subjects who are on prophylaxis INH therapy, and are slow to metabolic acetylation.
- Published
- 2021
42. Use of triazolam and alprazolam as premedication for general anesthesia
- Author
-
Doyun Kim, Seongheon Lee, Taehee Pyeon, and Seongwook Jeong
- Subjects
alprazolam ,amnesia ,premedication ,triazolam ,Anesthesiology ,RD78.3-87.3 - Abstract
BackgroundTriazolam has similar pharmacological properties as other benzodiazepines and is generally used as a sedative to treat insomnia. Alprazolam represents a possible alternative to midazolam for the premedication of surgical patients. The purpose of this study was to evaluate the anxiolytic, sedative, and amnestic properties of triazolam and alprazolam as pre-anesthetic medications.MethodsSixty adult patients were randomly allocated to receive oral triazolam 0.25 mg or alprazolam 0.5 mg one hour prior to surgery. A structured assessment interview was performed in the operating room (OR), the recovery room, and the ward. The levels of anxiety and sedation were assessed on a 7-point scale (0 = relaxation to 6 = very severe anxiety) and a 5-point scale (0 = alert to 4 = lack of responsiveness), respectively. The psychomotor performance was estimated using a digit symbol substitution test. As a memory test, we asked the patients the day after the surgery if they remembered being moved from the ward to the OR, and what object we had shown them in the OR.ResultsThere were no significant differences between the groups with respect to anxiety and sedation. The postoperative interviews showed that 22.2% of the triazolam-treated patients experienced a loss of memory in the OR, against a 0% memory loss in the alprazolam-treated patients. In comparison with alprazolam 0.5 mg, triazolam 0.25 mg produced a higher incidence of amnesia without causing respiratory depression.ConclusionsOral triazolam 0.25 mg can be an effective preanesthetic medication for psychomotor performance.
- Published
- 2015
- Full Text
- View/download PDF
43. Insomnia in Elderly Patients: Recommendations for Pharmacological Management.
- Author
-
Abad, Vivien C. and Guilleminault, Christian
- Subjects
- *
MELATONIN , *TRYPTOPHAN , *ANTIHISTAMINES , *NEUROTRANSMITTERS , *VALERIANA officinalis , *DRUG therapy , *ZOLPIDEM , *DIPHENHYDRAMINE , *SEDATIVES , *TRIAZOLAM , *TEMAZEPAM , *DOXEPIN , *DRUG utilization , *DRUG toxicity , *INSOMNIA , *DRUG approval , *TREATMENT effectiveness , *SLEEP hygiene , *OLD age , *THERAPEUTICS - Abstract
Chronic insomnia affects 57% of the elderly in the United States, with impairment of quality of life, function, and health. Chronic insomnia burdens society with billions of dollars in direct and indirect costs of care. The main modalities in the treatment of insomnia in the elderly are psychological/behavioral therapies, pharmacological treatment, or a combination of both. Various specialty societies view psychological/behavioral therapies as the initial treatment intervention. Pharmacotherapy plays an adjunctive role when insomnia symptoms persist or when patients are unable to pursue cognitive behavioral therapies. Current drugs for insomnia fall into different classes: orexin agonists, histamine receptor antagonists, non-benzodiazepine gamma aminobutyric acid receptor agonists, and benzodiazepines. This review focuses on Food and Drug Administration (FDA)-approved drugs for insomnia, including suvorexant, low-dose doxepin, Z-drugs (eszopiclone, zolpidem, zaleplon), benzodiazepines (triazolam, temazepam), and ramelteon. We review the indications, dosing, efficacy, benefits, and harms of these drugs in the elderly, and discuss data on drugs that are commonly used off-label to treat insomnia, and those that are in clinical development. The choice of a hypnotic agent in the elderly is symptom-based. Ramelteon or short-acting Z-drugs can treat sleep-onset insomnia. Suvorexant or low-dose doxepin can improve sleep maintenance. Eszopiclone or zolpidem extended release can be utilized for both sleep onset and sleep maintenance. Low-dose zolpidem sublingual tablets or zaleplon can alleviate middle-of-the-night awakenings. Benzodiazepines should not be used routinely. Trazodone, a commonly used off-label drug for insomnia, improves sleep quality and sleep continuity but carries significant risks. Tiagabine, sometimes used off-label for insomnia, is not effective and should not be utilized. Non-FDA-approved hypnotic agents that are commonly used include melatonin, diphenhydramine, tryptophan, and valerian, despite limited data on benefits and harms. Melatonin slightly improves sleep onset and sleep duration, but product quality and efficacy may vary. Tryptophan decreases sleep onset in adults, but data in the elderly are not available. Valerian is relatively safe but has equivocal benefits on sleep quality. Phase II studies of dual orexin receptor antagonists (almorexant, lemborexant, and filorexant) have shown some improvement in sleep maintenance and sleep continuity. Piromelatine may improve sleep maintenance. Histamine receptor inverse agonists (APD-125, eplivanserin, and LY2624803) improve slow-wave sleep but, for various reasons, the drug companies withdrew their products. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
44. The maxillary nerve block for in-office hybrid balloon sinus dilation procedures: A preliminary study.
- Author
-
Nishioka, Gary J.
- Subjects
- *
ANESTHESIA , *CATHETERIZATION , *ENDOSCOPIC surgery , *LOCAL anesthetics , *ORAL drug administration , *CUTANEOUS therapeutics , *PAIN management , *TRIAZOLAM , *MAXILLARY nerve - Abstract
Transitioning of rhinologic procedures from the operating room to the office setting in selected patients is a rising trend. An effective pain-control, patient-preparation protocol is essential, especially with advanced in-office rhinologic procedures such as hybrid balloon sinus dilation (BSD), in which other procedures such as ethmoidectomy, turbinate reduction, and other procedures are concomitantly performed. A regimen using oral sedation, topical tetracaine gel, topical tetracaine/epinephrine-soaked cottonoid packs, and intranasal local infiltrative anesthesia can vary significantly in effectiveness and be suboptimal at times (as determined by using treated patients as historical controls). A modification of this regimen was subsequently used, incorporating the maxillary nerve block, and qualitative differences were then assessed retrospectively between the two regimens. Twenty-five consecutive patients were retrospectively studied who underwent hybrid BSD procedures in the office setting using the maxillary nerve-block regimen modification. All patients underwent BSD of the sphenoid, frontal, and maxillary sinuses with anterior and partial posterior ethmoidectomies. Five patients also underwent septoplasty, and 18 patients underwent inferior turbinate reduction procedures. Twenty-four patients received oral sedation, and all patients received topical tetracaine/ epinephrine‑soaked cottonoid packs. The topical tetracaine gel was dropped after 5 patients because it was not felt to be needed anymore. No intranasal local infiltrative anesthesia was used. Several qualitative differences were observed after modifying the patient-preparation regimen incorporating the maxillary nerve block. The most important observation seen with this modification was a consistently reproducible, dense anesthesia coverage over the entire nasal cavity with good paranasal sinus coverage. This modification eliminated intranasal bleeding and swelling associated with intranasal local anesthetic injections. No complications were encountered. This preliminary study provides support for use and further evaluation of the maxillary nerve block for in-office rhinologic procedures. If the trend continues to rise in performing advanced in-office rhinologic procedures in selected patients, the maxillary nerve block may find a place in the patient-preparation protocol. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
45. Rapid determination of eight benzodiazepines in suspected counterfeit pharmaceuticals using surface‐enhanced Raman scattering with handheld Raman spectrometers
- Author
-
JaCinta S. Batson, Martin M. Kimani, and Adam Lanzarotta
- Subjects
Benzodiazepine ,Triazolam ,Chromatography ,Materials science ,Temazepam ,medicine.drug_class ,Capsules ,Lorazepam ,Spectrum Analysis, Raman ,Estazolam ,Injections ,Pathology and Forensic Medicine ,Benzodiazepines ,Cmin ,symbols.namesake ,Alprazolam ,Counterfeit Drugs ,Genetics ,medicine ,symbols ,Humans ,Raman spectroscopy ,Tablets ,medicine.drug - Abstract
The excessive prescription of benzodiazepines is putting more people at risk of dependence on these drugs and is exacerbating the fatal overdose toll of opioids. A rapid and sensitive SERS method has been developed for trace detection of select benzodiazepines in low-dosage suspect counterfeit tablets, capsules, and injectable solutions using two different portable handheld Raman spectrometers equipped with either a 785-nm laser or a 1064-nm laser. A total of 169 samples and blanks were examined using five handheld Raman spectrometers, which provided data set of 729 examinations. The extraction/SERS procedures yielded true positive rates above 90% for alprazolam, diazepam, and midazolam using the 1064-nm device and yielded true positive rates above 95% for alprazolam, clonazepam, diazepam, estazolam, midazolam, and temazepam using the 785-nm device; however, the extraction/SERS procedures yielded true positive rates below 60% for lorazepam and triazolam. The minimum concentration (Cmin ) of the benzodiazepine standards that reproducibly yielded a positive match ranged from 1 to 10 μg/ml using the 1064-nm laser device and from 0.5 to 50 μg/ml using the 785-nm laser device. For the analysis of authentic and suspect counterfeit tablets containing these benzodiazepines, the measured Cmin ranged between 10 and 15 µg per tablet or capsule for 1064-nm laser device and 1-100 µg per tablet or capsule for 785-nm laser device. The developed methods are simple, rapid, and ideal for screening suspect benzodiazepine-containing pharmaceutical products at satellite laboratories located within or near international mail facilities and express courier hubs.
- Published
- 2021
46. Comparison of Dental Benzodiazepine Prescriptions From the U.S., England, and Australia From 2013 to 2018
- Author
-
Leanne Teoh, Walid F. Gellad, Katie J. Suda, Wendy Thompson, Kathryn Finn, and Colin C. Hubbard
- Subjects
medicine.medical_specialty ,Triazolam ,Epidemiology ,medicine.drug_class ,Population ,Drug Prescriptions ,01 natural sciences ,Article ,Benzodiazepines ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,030212 general & internal medicine ,Practice Patterns, Physicians' ,0101 mathematics ,Medical prescription ,education ,Benzodiazepine ,education.field_of_study ,business.industry ,Temazepam ,010102 general mathematics ,Australia ,Public Health, Environmental and Occupational Health ,Lorazepam ,medicine.disease ,Analgesics, Opioid ,Substance abuse ,England ,Alprazolam ,Family medicine ,business ,medicine.drug - Abstract
Introduction Benzodiazepines contribute to substance use disorder and are often part of polydrug abuse, most frequently with opioids. Although dental opioid prescribing differs significantly between countries, little is known about the patterns of dental benzodiazepine prescribing. The aim of this study is to compare dental prescribing of benzodiazepines among the U.S., England, and Australia in 2013–2018. Methods Population-level data were accessed from national data sets for each country for dental benzodiazepine prescriptions. Outcome measures of dental benzodiazepine prescribing included: (1) prescribing rates by population for each year and (2) the quantity and relative proportion of benzodiazepines by type for each country. The analysis was conducted in 2020. Results Between 2013 and 2018, U.S. dentists prescribed 23 times more than English dentists and 7 times more than Australian dentists by population. During the study period, the rate of dental benzodiazepine prescribing decreased in England and the U.S. but increased in Australia. Despite these trends, U.S. dental prescribing rates remained 28 times more than English dentists and 6 times more than Australian dentists in 2018 (U.S., 3.10 prescriptions/1,000 population; England, 0.11 prescriptions/1,000 population; Australia, 0.50 prescriptions/1,000 population). U.S. dentists prescribed a wider variety of benzodiazepines than English and Australian dentists. Diazepam was most commonly prescribed in all countries. In the U.S., triazolam, lorazepam, and alprazolam were next most commonly prescribed. Temazepam was next most frequent in England and Australia. Conclusions Significant variation in benzodiazepine prescribing rates and types were seen among the countries. To improve patient safety, further investigation into the appropriate use and choices of benzodiazepines in dentistry is needed.
- Published
- 2021
47. Formulation and evaulation of triazolam odts by direct compression forselection & optimization of super disintegrates
- Author
-
Sudhakar Kancharla, Prachetha Kolli, and Dr.K.Venkata Gopaiah
- Subjects
Croscarmellose sodium ,Materials science ,Triazolam ,Compression (physics) ,Compression method ,chemistry.chemical_compound ,Tableting ,chemistry ,Methyl cellulose ,medicine ,Drug release ,Patient compliance ,Nuclear chemistry ,medicine.drug - Abstract
Oral Disintegrating Tablets of Triazolam were formulated with an aim to improve the versatility, patient compliance, and accurate dosing. The formulations ere developed with an objective to use by the pediatric and geriatric patients. Triazolam Oral Disintegrating Tablets were prepared by direct compression method using cross povidone, croscarmellose sodium, sodium starch glycolate and combinations of CP+CCS, and CP + SSG as super disintegrates exhibited good pre-formulation and tableting properties of three super disintegrates, the formulation contained combination of CP + CCS showed better performance in terms of disintegration time when compared to other formulations. Order of the super disintegrates activity is as follows. (CP + CCS) > (CP + SSG) > CP > CCS >SSG The formulation F15 was found to be the best among all twenty Triazolam ODT formulations because it has exhibited faster disintegration time (17.66 sec) when compared to the other formulations and it showed 99.87±0.18% drug release at the end of 25 min. Triazolam Oral Disintegrating Films were prepared by solvent casting method using different grades of Hydroxypropyl Methyl Cellulose like HPMC – E15, HPMC – 5cps, HPMC – 50cps. Based on disintegration and dissolution results it was concluded that the formulation F15 contained CP 5% + CCS 5% was the best formulation among all otherformulations.
- Published
- 2021
48. Human anxiety-specific 'theta' occurs with selective stopping and localizes to right inferior frontal gyrus
- Author
-
Bede Byers, Paul Glue, Olivia High, Shabah M. Shadli, Rubina Steller, Neil McNaughton, and Polly Gibbs
- Subjects
Adult ,Male ,Triazolam ,Adolescent ,Pregabalin ,Prefrontal Cortex ,Hippocampus ,Electroencephalography ,Stop signal ,Buspirone ,Young Adult ,Behavioral Neuroscience ,Reaction Time ,medicine ,Humans ,0501 psychology and cognitive sciences ,050102 behavioral science & comparative psychology ,Theta Rhythm ,Neuroticism ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Anxiety Disorders ,Inhibition, Psychological ,Anti-Anxiety Agents ,Anxiety ,Female ,medicine.symptom ,business ,Neuroscience ,Biomarkers ,medicine.drug - Abstract
Anxiety disorders have high prevalence and generate major disability. But they have poor treatment targeting because psychiatry lacks diagnostic biomarkers. Right frontal goal-conflict-specific-rhythmicity (GCSR) in the simple stop signal task appears homologous to hippocampal "theta" as an anxiety-process biomarker but is weak and transient. An anticipatory response inhibition task (ARIT) elicits strong subjective conflict and so might generate stronger GCSR. Healthy participants provided EEG during an ARIT, which allowed direct comparison of selective (left, SG; right, GS), and nonselective (both, SS) handed stopping. We assessed GCSR as intermediate versus the average of short and long delay stop-specific power. SG produced right frontal 5-12 Hz GCSR that, as in the SST: significantly correlated with trait anxiety and neuroticism; and was sensitive to pregabalin (75 mg), buspirone (10 mg), and perhaps triazolam (0.25 mg). GS and SS produced faster stopping and only 9-10Hz GCSR, which did not correlate significantly with trait anxiety or neuroticism and was sensitive to pregabalin and buspirone but not triazolam. Source localization suggested that GCSR, like stopping, involves multiple right frontal circuits that depend on response speed. Anxiolytic-sensitive GCSR generalizes from the speeded stop signal task to fixed-time anticipatory response inhibition tasks. GCSR, and the circuits engaged, vary with stop signal RTs conditions. Tasks with longer stop times may be optimal to generate GCSR homologous with rodent hippocampal theta as (a) the first direct anchor of a specific neural form of trait anxiety; (b) a single-dose screen in normal humans for novel anxiolytics; and (c) a potential clinical anxiety biomarker. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
- Published
- 2020
49. Effects of different doses of triazolam in the middle-of-the-night insomnia: a double-blind, randomized, parallel group study.
- Author
-
Ferini Strambi, Luigi, Marelli, Sara, Zucconi, Marco, Galbiati, Andrea, and Biggio, Giovanni
- Subjects
- *
TRIAZOLAM , *INSOMNIA treatment , *RAPID eye movement sleep , *SLEEP disorders treatment , *POLYSOMNOGRAPHY , *PHYSIOLOGY , *THERAPEUTICS ,AGE factors in insomnia - Abstract
It has been reported that insomnia characterized by difficulty returning to sleep following a nocturnal awakening, otherwise defined as the middle-of-the-night (MOTN) insomnia, is a common form of insomnia in adults with growing prevalence by increasing age. The aim of this study is to evaluate the efficacy and safety of different dosages of triazolam in insomnia patients when taken after a MOTN awakening with difficulty returning to sleep. In this double-blind, randomized, parallel group study, 24 patients (mean age 41.00 ± 10.40, 10 female and 14 male) affected by MOTN insomnia were enrolled and randomized into three groups according to different dosages of triazolam: group A (0.0625 mg), group B (0.125 mg), and group C (0.250 mg). A significant increment of total sleep time, sleep efficiency and a reduction of wake after sleep onset, number of awakening and non-REM sleep stage 1 was observed in T1 (triazolam) in comparison to T0 (placebo) by means of polysomnographic recording, irrespective of dosage. After 2 weeks of the treatment, insomnia severity significantly improved in all three groups in comparison to baseline without diurnal residual effects. This study demonstrates that low dose of triazolam objectively and subjectively improves the sleep of patients having MOTN insomnia. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
50. Looking at flubromazolam metabolism from four different angles: Metabolite profiling in human liver microsomes, human hepatocytes, mice and authentic human urine samples with liquid chromatography high-resolution mass spectrometry.
- Author
-
Roman, Markus, Andersson, Mikael, Wohlfarth, Ariane, Kugelberg, Fredrik C., Green, Henrik, Kronstrand, Robert, and Vikingsson, Svante
- Subjects
- *
METABOLITE analysis , *TRIAZOLAM , *MASS spectrometry , *METABOLISM , *BENZODIAZEPINES , *LIQUID chromatography - Abstract
Flubromazolam is a triazolam benzodiazepine that recently emerged as a new psychoactive substance. Since metabolism data are scarce and good analytical targets besides the parent are unknown, we investigated flubromazolam metabolism in vitro and in vivo. 10μmol/L flubromazolam was incubated with human liver microsomes for 1h and with cryopreserved human hepatocytes for 5h. Mice were administered 0.5 or 1.0mg flubromazolam/kg body weight intraperitoneally, urine was collected for 24h. All samples, together with six authentic forensic human case specimens, were analyzed (with or without hydrolysis, in case it was urine) by UHPLC-HRMS on an Acquity HSS T3 column with an Agilent 6550 QTOF. Data mining was performed manually and with MassMetasite software (Molecular Discovery). A total of nine metabolites were found, all generated by hydroxylation and/or glucuronidation. Besides O-glucuronidation, flubromazolam formed an N+-glucuronide. Flubromazolam was not metabolized extensively in vitro, as only two monohydroxy metabolites were detected in low intensity in hepatocytes. In the mice samples, seven metabolites were identified, which mostly matched the metabolites in the human samples. However, less flubromazolam N+-glucuronide and an additional hydroxy metabolite were observed. The six human urine specimens showed different extent of metabolism: some samples had an intense flubromazolam peak next to a minute signal for a monohydroxy metabolite, others showed the whole variety of hydroxylated and glucuronidated metabolites. Overall, the most abundant metabolite was a monohydroxy metabolite, which we propose as α-hydroxyflubromazolam based on MSMS fragmentation. These metabolism data will assist in interpretation and analytical method development. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.