20 results on '"Indomethacin pharmacokinetics"'
Search Results
2. Development of Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Indomethacin Disposition in Pregnancy.
- Author
-
Alqahtani, Saeed and Kaddoumi, Amal
- Subjects
PHARMACOKINETICS ,PHARMACODYNAMICS ,INDOMETHACIN ,BLOOD plasma ,MATERNAL health ,THERAPEUTICS - Abstract
Findings of a recent clinical study showed indomethacin has lower plasma levels and higher steady-state apparent clearance in pregnant subjects when compared to those in non-pregnant subjects reported in separate studies. Thus, in the current work we developed a pregnancy physiological based pharmacokinetic/pharmacodynamic (PBPK/PD) model for indomethacin to explain the differences in indomethacin pharmacokinetics between pregnancy and non-pregnancy. A whole-body PBPK model with key pregnancy-related physiological changes was developed to characterize indomethacin PK in pregnant women and compare these parameters to those in non-pregnant subjects. Data related to maternal physiological and biological changes were obtained from literature and incorporated into the structural PBPK model that describes non-pregnant PK data. Changes in indomethacin area under the curve (AUC), maximum concentration (C
max ) and average steady-state concentration (Cave ) in pregnant women were predicted. Model-simulated PK profiles were in agreement with observed data. The predicted mean ratio (non-pregnant:second trimester (T2 )) of indomethacin Cave was 1.6 compared to the observed value of 1.59. In addition, the predicted steady-state apparent clearance (CL/Fss ) ratio was almost similar to the observed value (0.46 vs. 0.42). Sensitivity analysis suggested changes in CYP2C9 activity, and to a lesser extent UGT2B7, as the primary factor contributing to differences in indomethacin disposition between pregnancy and non-pregnancy. The developed PBPK model which integrates prior physiological knowledge, in vitro and in vivo data, allowed the successful prediction of indomethacin disposition during T2 . Our PBPK/PD model suggested a higher indomethacin dosing requirement during pregnancy. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
3. Review on the protective activity of osthole against the pathogenesis of osteoporosis.
- Author
-
Jincai Chen, Xiaofei Liao, and Juwen Gan
- Subjects
OSTEOPOROSIS ,BONE resorption ,BONE growth ,DRUG target ,COUMARIN derivatives ,WNT signal transduction - Abstract
Osteoporosis (OP), characterized by continuous bone loss and increased fracture risk, has posed a challenge to patients and society. Long-term administration of current pharmacological agents may cause severe side effects. Traditional medicines, acting as alternative agents, show promise in treating OP. Osthole, a natural coumarin derivative separated from Cnidium monnieri (L.) Cusson and Angelica pubescens Maxim. f., exhibits protective effects against the pathological development of OP. Osthole increases osteoblast-related bone formation and decreases osteoclast-related bone resorption, suppressing OP-related fragility fracture. In addition, the metabolites of osthole may exhibit pharmacological effectiveness against OP development. Mechanically, osthole promotes osteogenic differentiation by activating the Wnt/β-catenin and BMP-2/Smad1/5/8 signaling pathways and suppresses RANKL-induced osteoclastogenesis and osteoclast activity. Thus, osthole may become a promising agent to protect against OP development. However, more studies should be performed due to, at least in part, the uncertainty of drug targets. Further pharmacological investigation of osthole in OP treatment might lead to the development of potential drug candidates. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
4. Developmental pharmacokinetics of indomethacin in preterm neonates: Severely decreased drug clearance in the first week of life.
- Author
-
Krzyzanski, Wojciech, Stockard, Bradley, Gaedigk, Andrea, Scott, Allison, Nolte, Whitney, Gibson, Kim, Leeder, J. Steven, and Lewis, Tamorah
- Subjects
NEONATAL intensive care units ,INDOMETHACIN ,NEWBORN infants ,PHARMACOKINETICS ,INTRACRANIAL hemorrhage - Abstract
Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently was tested for accuracy in a validation cohort. Postnatal age was a significant covariate for hepatic clearance (CLH) and renal clearance (CLR). The typical value of the total clearance (CL, the sum of CLR and CLH) was 3.09 ml/h and expressed as CL/WTmedian = 3.96 ml/h/kg, where WTmedian is the median body weight. The intersubject variability of CLR and CLH were 61% and 207%, respectively. The typical value of the volume of distribution Vp = 366 ml (Vp/WTmedian = 470 ml/kg), and its intersubject variability was 38.8%. Half‐life was 82.1 h. Compared with more mature and older preterm populations studied previously, indomethacin CL is considerably lower in this contemporary population. Model‐informed precision dosing incorporating important covariates other than weight alone offers an opportunity to individualize dosing in a susceptible patient undergoing rapid change. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. Bidirectional interactions between indomethacin and the murine intestinal microbiota.
- Author
-
Xue Liang, Bittinger, Kyle, Xuanwen Li, Abernethy, Darrell R., Bushman, Frederic D., and FitzGerald, Garret A.
- Subjects
- *
INDOMETHACIN , *XENOBIOTICS , *ANTI-inflammatory agents , *CYCLOOXYGENASES , *PHARMACODYNAMICS , *DOSE-effect relationship in pharmacology , *PHARMACOKINETICS , *LABORATORY mice , *THERAPEUTICS - Abstract
The vertebrate gut microbiota have been implicated in the metabolism of xenobiotic compounds, motivating studies of microbe-driven metabolism of clinically important drugs. Here, we studied interactions between the microbiota and indomethacin, a nonsteroidal anti- inflammatory drug (NSAID) that inhibits cyclooxygenases (COX) -1 and -2. Indomethacin was tested in both acute and chronic exposure models in mice at clinically relevant doses, which suppressed production of COX-1- and COX-2-derived prostaglandins and caused small intestinal (SI) damage. Deep sequencing analysis showed that indomethacin exposure was associated with alterations in the structure of the intestinal microbiota in both dosing models. Perturbation of the intestinal microbiome by antibiotic treatment altered indomethacin pharmacokinetics and pharmacodynamics, which is probably the result of reduced bacterial β-glucuronidase activity. Humans show considerable inter-individual differences in their microbiota and their responses to indomethacin — thus, the drug-microbe interactions described here provide candidate mediators of individualized drug responses. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
6. Safety Profile of Nutraceuticals Rich in Coumarins: An Update.
- Author
-
Heghes, Simona Codruta, Vostinaru, Oliviu, Mogosan, Cristina, Miere, Doina, Iuga, Cristina Adela, and Filip, Lorena
- Subjects
COUMARINS ,EXPOSURE dose ,PLANT species ,PLANT roots ,HOME furnishings ,FUNCTIONAL foods - Abstract
Coumarins are a family of benzopyrones largely distributed in the natural kingdom, being present in the seeds, fruits, flowers, or roots of various plant species. Natural coumarin compounds are found in significant concentrations in some herbs or spices used as nutraceuticals, but they are also present in cosmetics or household products, due to their pleasant odor. Therefore, an accidental exposure to high doses of coumarins, could lead to the development of harmful effects in some patients. This review summarizes the latest published data from preclinical and clinical studies with natural coumarins, focused on the investigation of general and specific toxicity, with the aim of a better understanding of the safety profile of these valuable compounds. Regulatory aspects concerning the use of natural coumarins in several world regions are also reviewed. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
7. Impact of non-antibiotic drugs on the human intestinal microbiome.
- Author
-
Le Bastard, Quentin, Berthelot, Laureline, Soulillou, Jean-Paul, and Montassier, Emmanuel
- Abstract
The gut microbiota is composed of trillions of microbial cells and viruses that interact with hosts. The composition of the gut microbiota is influenced by several factors including age, diet, diseases, or medications. The impact of drugs on the microbiota is not limited to antibiotics and many non-antibiotic molecules significantly alter the composition of the intestinal microbiota. This review focuses on the impact of four of the most widely prescribed non-antibiotic drugs in the world: Proton-pump inhibitors, metformin, statins, and non-steroidal anti-inflammatory. We conducted a systematic review by searching online databases including Medline, Web of science, and Scopus for indexed articles published in English until February 2021. We included studies assessing the intestinal microbiome alterations associated with proton pump inhibitors (PPIs), metformin, statins, and nonsteroidal anti-inflammatory drugs (NSAIDs). Only studies using culture-independent molecular techniques were included. The taxonomical signature associated with non-antibiotic drugs are not yet fully described, especially in the field of metabolomic. The identification of taxonomic profiles associated a specific molecule provides information on its mechanism of action through interaction with the intestinal microbiota. Many side effects could be related to the dysbiosis induced by these molecules. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
8. A preliminary study on pharmacokinetics of oral indomethacin in premature infants in north India
- Author
-
P K, Sharma, S K, Garg, and A, Narang
- Subjects
Male ,Indomethacin ,Infant, Newborn ,Administration, Oral ,Birth Weight ,Humans ,India ,Cardiovascular Agents ,Female ,Ductus Arteriosus, Patent ,Infant, Premature - Abstract
Patent ductus arteriosus (PDA) is a frequent complication in premature infants. Intravenous indomethacin is the standard mode of medical therapy and has been shown to be efficacious in closing the ductus. In our setup, oral indomethacin is being regularly used for medical treatment of suspected or clinically diagnosed PDA. Non-availability of the parenteral preparation and lack of information regarding the pharmacokinetic disposition of indomethacin in the premature infants in north Indian population led us to conduct this pharmacokinetic study with oral indomethacin.Twenty premature infants with gestational age 30.3 +/- 0.3 wk and birth weight, 1209.8 +/- 39.5 g; admitted to the neonatal unit of the Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh were enrolled in the study. Indomethacin was administered in a single oral dose of 0.2 mg/kg and blood samples were collected through an indwelling vascular catheter at 0 and 1, 2, 4, 8 and 12 h after administration of indomethacin. Plasma indomethacin concentrations were assayed by spectrofluorometric technique.Large interindividual variability was observed for peak plasma concentrations (Cmax; 137.9 +/- 14.0 ng/ml), elimination half-life (t1/2 el; 21.4 +/- 1.7 h) and area under the plasma concentrations time curve (AUC0-infinity;4172 +/- 303 ng.h/ml) in these infants. Variables like birth weight, and sex did not have any sigiificant effect on indomethacin pharmacokinetics. However, the plasma t1/2 el of indomethacin was significantly (P0.01) larger in older infants (gestational age30 wk) in comparison to younger ones (gestational ageor = 30 wk). There was a negative correlation between gestational age and elimination t1/2 (r = -0.77).In conclusion, indomethacin pharmacokinetics showed a wide variability in premature infants. In view of these findings it can be suggested that infants of smaller gestational age are at greater risk of cumulative toxicity if more than one dose of indomethacin is given. With advancing age, metabolism as well as elimination of drug is faster that may require modification in indomethacin dose to achieve therapeutic response. These preliminary results may be of use in designing future pharmacokinetic studies of oral indomethacin in preterm neonates on a larger sample.
- Published
- 2003
9. Development of Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Indomethacin Disposition in Pregnancy.
- Author
-
Saeed Alqahtani and Amal Kaddoumi
- Subjects
Medicine ,Science - Abstract
Findings of a recent clinical study showed indomethacin has lower plasma levels and higher steady-state apparent clearance in pregnant subjects when compared to those in non-pregnant subjects reported in separate studies. Thus, in the current work we developed a pregnancy physiological based pharmacokinetic/pharmacodynamic (PBPK/PD) model for indomethacin to explain the differences in indomethacin pharmacokinetics between pregnancy and non-pregnancy. A whole-body PBPK model with key pregnancy-related physiological changes was developed to characterize indomethacin PK in pregnant women and compare these parameters to those in non-pregnant subjects. Data related to maternal physiological and biological changes were obtained from literature and incorporated into the structural PBPK model that describes non-pregnant PK data. Changes in indomethacin area under the curve (AUC), maximum concentration (Cmax) and average steady-state concentration (Cave) in pregnant women were predicted. Model-simulated PK profiles were in agreement with observed data. The predicted mean ratio (non-pregnant:second trimester (T2)) of indomethacin Cave was 1.6 compared to the observed value of 1.59. In addition, the predicted steady-state apparent clearance (CL/Fss) ratio was almost similar to the observed value (0.46 vs. 0.42). Sensitivity analysis suggested changes in CYP2C9 activity, and to a lesser extent UGT2B7, as the primary factor contributing to differences in indomethacin disposition between pregnancy and non-pregnancy. The developed PBPK model which integrates prior physiological knowledge, in vitro and in vivo data, allowed the successful prediction of indomethacin disposition during T2. Our PBPK/PD model suggested a higher indomethacin dosing requirement during pregnancy.
- Published
- 2015
- Full Text
- View/download PDF
10. Neonatal pain management.
- Author
-
Bhalla, Tarun, Shepherd, Ed, and Tobias, Joseph D.
- Subjects
PAIN management ,NEWBORN infant health ,CENTRAL nervous system abnormalities ,NEONATAL anesthesia ,OPIOIDS - Abstract
The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
11. Biopharmaceutics of Topical Ophthalmic Suspensions: Importance of Viscosity and Particle Size in Ocular Absorption of Indomethacin.
- Author
-
Toropainen, Elisa, Fraser-Miller, Sara J., Novakovic, Dunja, Del Amo, Eva M., Vellonen, Kati-Sisko, Ruponen, Marika, Viitala, Tapani, Korhonen, Ossi, Auriola, Seppo, Hellinen, Laura, Reinisalo, Mika, Tengvall, Unni, Choi, Stephanie, Absar, Mohammad, Strachan, Clare, Urtti, Arto, and Otero-Espinar, Francisco Javier
- Subjects
INDOMETHACIN ,BIOPHARMACEUTICS ,VISCOSITY ,DRUG solubility ,AQUEOUS humor ,TEARS (Body fluid) - Abstract
Eye drops of poorly soluble drugs are frequently formulated as suspensions. Bioavailability of suspended drug depends on the retention and dissolution of drug particles in the tear fluid, but these factors are still poorly understood. We investigated seven ocular indomethacin suspensions (experimental suspensions with two particle sizes and three viscosities, one commercial suspension) in physical and biological tests. The median particle size (d
50 ) categories of the experimental suspensions were 0.37–1.33 and 3.12–3.50 µm and their viscosity levels were 1.3, 7.0, and 15 mPa·s. Smaller particle size facilitated ocular absorption of indomethacin to the aqueous humor of albino rabbits. In aqueous humor the AUC values of indomethacin suspensions with different particle sizes, but equal viscosity, differed over a 1.5 to 2.3-fold range. Higher viscosity increased ocular absorption 3.4–4.3-fold for the suspensions with similar particle sizes. Overall, the bioavailability range for the suspensions was about 8-fold. Instillation of larger particles resulted in higher tear fluid AUC values of total indomethacin (suspended and dissolved) as compared to application of smaller particles. Despite these tear fluid AUC values of total indomethacin, instillation of the larger particles resulted in smaller AUC levels of indomethacin in the aqueous humor. This suggests that the small particles yielded higher concentrations of dissolved indomethacin in the tear fluid, thereby leading to improved ocular bioavailability. This new conclusion was supported by ocular pharmacokinetic modeling. Both particle size and viscosity have a significant impact on drug concentrations in the tear fluid and ocular drug bioavailability from topical suspensions. Viscosity and particle size are the key players in the complex interplay of drug retention and dissolution in the tear fluid, thereby defining ocular drug absorption and bioequivalence of ocular suspensions. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
12. pH-Dependent passive and active transport of acidic drugs across Caco-2 cell monolayers
- Author
-
Neuhoff, Sibylle, Ungell, Anna-Lena, Zamora, Ismael, Artursson, Per, Neuhoff, Sibylle, Ungell, Anna-Lena, Zamora, Ismael, and Artursson, Per
- Abstract
The aim of this study was to investigate pH-dependent passive and active transport of acidic drugs across Caco-2 cells. Therefore, the bidirectional pH-dependent transport of two acidic drugs, indomethacin and salicylic acid, across Caco-2 cells was studied in the physiological pH range of the gastrointestinal tract. The transport of both drugs decreased with increased pH, as expected from the pH-partition hypothesis. Net absorption occurred when the basolateral pH exceeded the apical pH. Concentration dependence and transporter inhibition studies indicated passive transport for indomethacin and a mixture of pH-dependent passive and active influx for salicylic acid. Unexpectedly, active and passive drug transport results were indistinguishable in temperature dependency studies. The transport of salicylic acid (apical pH 5.0; basolateral pH 7.4) was partly blocked by inhibitors of the proton-dependent transporters MCT1 (SLC16A1) and OATP-B (SLC21A9, SLCO2B1). This study shows that the asymmetry in bidirectional transport of acidic drugs is affected by both passive and active components in the presence of pH gradients across Caco-2 cells. Thus, combined studies of concentration-dependency and transport-inhibition are preferred when acidic drug transport is studied in a pH gradient. The findings of this in vitro study can be extrapolated to in vivo situations involving an acidic microclimate.
- Published
- 2005
- Full Text
- View/download PDF
13. Timing of perioperative non-steroidal anti-inflammatory drug treatment
- Author
-
Camu, Frédéric, Vanlersberghe, Caroline, Lauwers, Marylin, Camu, Frédéric, Vanlersberghe, Caroline, and Lauwers, Marylin
- Abstract
The time of non-steroidal antiinflammatory drug (NSAID) administration may be clinically important because their onset of effect may be delayed by 30-60 minutes while their opioid sparing effect is not apparent until 4 hours after administration. These findings can be explained by the pharmacokinetic behavior of these agents. Numerous studies addressing the short-term benefit of preemptive administration of NSAIDs gave inconclusive results, in part due to the study design. But if a preemptive analgesic effect of NSAIDs was demonstrated in some studies, it was of short duration and had no significant clinical benefit. Also, the risks associated with preoperative NSAID administration, such as operative site bleeding,should be considered against the potential benefits in establishing a treatment regimen., SCOPUS: cp.j, info:eu-repo/semantics/published
- Published
- 1996
14. Development of Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Indomethacin Disposition in Pregnancy
- Author
-
Amal Kaddoumi and Saeed Alqahtani
- Subjects
Pregnancy ,Physiologically based pharmacokinetic modelling ,Multidisciplinary ,business.industry ,lcsh:R ,Anti-Inflammatory Agents, Non-Steroidal ,Indomethacin ,Area under the curve ,Cmax ,lcsh:Medicine ,Pharmacology ,medicine.disease ,Models, Biological ,UGT2B7 ,Pharmacokinetics ,In vivo ,Pharmacodynamics ,Medicine ,Humans ,lcsh:Q ,Female ,business ,lcsh:Science ,Research Article - Abstract
Findings of a recent clinical study showed indomethacin has lower plasma levels and higher steady-state apparent clearance in pregnant subjects when compared to those in non-pregnant subjects reported in separate studies. Thus, in the current work we developed a pregnancy physiological based pharmacokinetic/pharmacodynamic (PBPK/PD) model for indomethacin to explain the differences in indomethacin pharmacokinetics between pregnancy and non-pregnancy. A whole-body PBPK model with key pregnancy-related physiological changes was developed to characterize indomethacin PK in pregnant women and compare these parameters to those in non-pregnant subjects. Data related to maternal physiological and biological changes were obtained from literature and incorporated into the structural PBPK model that describes non-pregnant PK data. Changes in indomethacin area under the curve (AUC), maximum concentration (Cmax) and average steady-state concentration (Cave) in pregnant women were predicted. Model-simulated PK profiles were in agreement with observed data. The predicted mean ratio (non-pregnant:second trimester (T2)) of indomethacin Cave was 1.6 compared to the observed value of 1.59. In addition, the predicted steady-state apparent clearance (CL/Fss) ratio was almost similar to the observed value (0.46 vs. 0.42). Sensitivity analysis suggested changes in CYP2C9 activity, and to a lesser extent UGT2B7, as the primary factor contributing to differences in indomethacin disposition between pregnancy and non-pregnancy. The developed PBPK model which integrates prior physiological knowledge, in vitro and in vivo data, allowed the successful prediction of indomethacin disposition during T2. Our PBPK/PD model suggested a higher indomethacin dosing requirement during pregnancy.
- Published
- 2015
15. The effect of allopurinol on the steady-state pharmacokinetics of indomethacin.
- Author
-
Pullar, T., Myall, O., Haigh, J.R., Lowe, J.R., Dixon, JS, and Bird, HA
- Abstract
The effect of 5 days treatment with allopurinol (300 mg) on the pharmacokinetics of indomethacin at steady-state was investigated in eight patients. Allopurinol produced no significant effect on the indomethacin serum concentration-time curve. Allopurinol did not alter significantly the amounts of indomethacin excreted in the urine within 8 h. However, the urinary ratio of N-deschlorobenzoylindomethacin to indomethacin was reduced significantly by allopurinol administration (P less than 0.05). [ABSTRACT FROM AUTHOR]
- Published
- 1988
- Full Text
- View/download PDF
16. Pharmacokinetics of digoxin alone and in the presence of indomethacin therapy.
- Author
-
Finch, MB, Johnston, GD, Kelly, JG, and McDevitt, DG
- Abstract
The effects of maintenance indomethacin therapy on single dose digoxin pharmacokinetics and dynamics were studied in six healthy volunteers with normal renal function. Indomethacin did not alter the elimination half-life, systemic clearance or distribution of digoxin. No pharmacodynamic interaction as assessed by changes in the systolic time intervals QA2 and LVET was found. This study does not lend support for a significant digoxin-indomethacin interaction in man. [ABSTRACT FROM AUTHOR]
- Published
- 1984
- Full Text
- View/download PDF
17. Pharmacokinetics of indomethacin in chronic migraine patients after withdrawal from the overused combination of indomethacin, Prochlorperazine and caffeine
- Author
-
Anna Ferrari, Daniela Gallesi, Diego Pinetti, Grazia Sances, Emilio Sternieri, and Alfio Bertolini
- Subjects
Drug ,business.industry ,media_common.quotation_subject ,General Medicine ,Prochlorperazine ,medicine.disease ,Medication-overuse headache ,chemistry.chemical_compound ,Chronic Migraine ,INDOMETHACIN ,chemistry ,Migraine ,Pharmacokinetics ,Anesthesia ,medicine ,Analysis of variance ,Dosing ,Caffeine ,business ,Drug combination ,pharmacokinetics ,medicine.drug ,media_common ,Chronic migraine - Abstract
Indomethacin, in combination with prochlorperazine and caffeine (IPC), is often overused by migraine patients who develop medication-overuse headache. Indomethacin clearance is slower in chronic migraine patients overusing IPC combination than in migraine patients only occasionally taking it. The objective of this study was to verify if indomethacin reduced clearance reverted to normal values after withdrawal of the overused IPC combination. Therefore, we repeated the study of indomethacin pharmacokinetics in 9 female chronic migraine patients after 3 months from inpatient withdrawal treatment from IPC combination overuse. The IPC combination (indomethacin 50 mg, prochlorperazine 8 mg, caffeine 150 mg) habitually taken was administered by rectal route to each patient. Blood samples were drawn before dosing and at the following post-dose times: 0.5, 1, 2, 3, 4, and 6 h. Indomethacin concentrations were measured by HPLC method. We found that 4 of 9 patients (group A) who were still overusing the combination and suffering from daily headache had still high indomethacin concentrations after 6 hours, therefore showing a slow elimination of the drug. Instead, in the 5 patients (group B) who had discontinued overuse of IPC combination after withdrawal treatment, indomethacin concentrations after 6 hours were significantly lower than those measured before withdrawal (P < 0.05, Student’s t-test for paired data), and also than those observed in group A (P < 0.05, ANOVA and Newman-Keuls’test). Hence, by suspending IPC abuse indomethacin clearance reverts to normal values and this is associated with an improvement of migraine. Instead, the higher plasma levels of indomethacin in patients who continue IPC abuse do not solve migraine and might support medication-overuse headache.
- Published
- 2013
18. Reports from University of Louisiana Advance Knowledge in Pregnancy (Development of Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Indomethacin Disposition in Pregnancy)
- Subjects
Women's health -- Analysis -- Models ,Indomethacin -- Research -- Analysis -- Models ,Pregnancy -- Analysis -- Models ,Pregnant women -- Analysis -- Models ,Health ,Women's issues/gender studies - Abstract
2016 FEB 4 (NewsRx) -- By a News Reporter-Staff News Editor at Women's Health Weekly -- Researchers detail new data in Women's Health. According to news reporting out of Monroe, [...]
- Published
- 2016
19. Bidirectional interactions between indomethacin and the murine intestinal microbiota.
- Author
-
Liang X, Bittinger K, Li X, Abernethy DR, Bushman FD, and FitzGerald GA
- Subjects
- Animals, Biota drug effects, Biotransformation, Mice, Anti-Inflammatory Agents, Non-Steroidal metabolism, Gastrointestinal Microbiome drug effects, Indomethacin metabolism
- Abstract
The vertebrate gut microbiota have been implicated in the metabolism of xenobiotic compounds, motivating studies of microbe-driven metabolism of clinically important drugs. Here, we studied interactions between the microbiota and indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenases (COX) -1 and -2. Indomethacin was tested in both acute and chronic exposure models in mice at clinically relevant doses, which suppressed production of COX-1- and COX-2-derived prostaglandins and caused small intestinal (SI) damage. Deep sequencing analysis showed that indomethacin exposure was associated with alterations in the structure of the intestinal microbiota in both dosing models. Perturbation of the intestinal microbiome by antibiotic treatment altered indomethacin pharmacokinetics and pharmacodynamics, which is probably the result of reduced bacterial β-glucuronidase activity. Humans show considerable inter-individual differences in their microbiota and their responses to indomethacin - thus, the drug-microbe interactions described here provide candidate mediators of individualized drug responses.
- Published
- 2015
- Full Text
- View/download PDF
20. A preliminary study on pharmacokinetics of oral indomethacin in premature infants in north India.
- Author
-
Sharma PK, Garg SK, and Narang A
- Subjects
- Administration, Oral, Birth Weight, Cardiovascular Agents therapeutic use, Ductus Arteriosus, Patent drug therapy, Female, Humans, India, Indomethacin therapeutic use, Infant, Newborn, Infant, Premature, Male, Cardiovascular Agents pharmacokinetics, Indomethacin pharmacokinetics
- Abstract
Background & Objectives: Patent ductus arteriosus (PDA) is a frequent complication in premature infants. Intravenous indomethacin is the standard mode of medical therapy and has been shown to be efficacious in closing the ductus. In our setup, oral indomethacin is being regularly used for medical treatment of suspected or clinically diagnosed PDA. Non-availability of the parenteral preparation and lack of information regarding the pharmacokinetic disposition of indomethacin in the premature infants in north Indian population led us to conduct this pharmacokinetic study with oral indomethacin., Methods: Twenty premature infants with gestational age 30.3 +/- 0.3 wk and birth weight, 1209.8 +/- 39.5 g; admitted to the neonatal unit of the Nehru Hospital, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh were enrolled in the study. Indomethacin was administered in a single oral dose of 0.2 mg/kg and blood samples were collected through an indwelling vascular catheter at 0 and 1, 2, 4, 8 and 12 h after administration of indomethacin. Plasma indomethacin concentrations were assayed by spectrofluorometric technique., Results: Large interindividual variability was observed for peak plasma concentrations (Cmax; 137.9 +/- 14.0 ng/ml), elimination half-life (t1/2 el; 21.4 +/- 1.7 h) and area under the plasma concentrations time curve (AUC0-infinity;4172 +/- 303 ng.h/ml) in these infants. Variables like birth weight, and sex did not have any sigiificant effect on indomethacin pharmacokinetics. However, the plasma t1/2 el of indomethacin was significantly (P < 0.01) larger in older infants (gestational age > 30 wk) in comparison to younger ones (gestational age < or = 30 wk). There was a negative correlation between gestational age and elimination t1/2 (r = -0.77)., Interpretation & Conclusion: In conclusion, indomethacin pharmacokinetics showed a wide variability in premature infants. In view of these findings it can be suggested that infants of smaller gestational age are at greater risk of cumulative toxicity if more than one dose of indomethacin is given. With advancing age, metabolism as well as elimination of drug is faster that may require modification in indomethacin dose to achieve therapeutic response. These preliminary results may be of use in designing future pharmacokinetic studies of oral indomethacin in preterm neonates on a larger sample.
- Published
- 2003
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