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World Health Organization (WHO) recommends the use of first-line anti-tuberculosis drugs, that is, rifampicin (RIF) and isoniazid (INH) fixed-dose combination (FDC) therapies in tuberculosis (TB) d...

The review deals with a new form of oral antidiabetic drugs with a fixed dose — the combination of sustained-release metformin and glimepiride. Amaryl®M SR (2/500 mg) — a new dosage form, which provides a rapid release of glimepiride, and then the slow release of metformin from multipolymer hydrophilic matrix independently of pH. Based on the research of therapeutic efficacy and bioavailability, it is shown that this form is characterized by an optimal pharmacokinetics of metformin and glimepiride, does not increase the incidence of hypoglycemia, may be administered once a day, and is associated with less severe gastrointestinal side effects, as well as has more pronounced compliance. Application of Amaryl®M SR creates new possibilities for patients with type 2 diabetes mellitus in terms of optimizing glycemic control and quality of life., Обзор посвящен новой форме пероральных антидиабетических препаратов с фиксированной дозой — комбинации метформина замедленного высвобождения и глимепирида. Амарил®М СР (2/500 мг) — новая лекарственная форма, обеспечивающая быстрое высвобождение глимепирида, а затем медленное высвобождение метформина из мультиполимерного гидрофильного матрикса независимо от рН. На основании исследования терапевтической эффективности и биодоступности показано, что данная форма характеризуется оптимальной фармакокинетикой метформина и глимепирида, не приводит к увеличению частоты гипогликемий, может назначаться однократно в сутки и ассоциирована с меньшей выраженностью желудочно-кишечных побочных эффектов, а также с большей приверженностью к лечению. Применение Амарила®М СР создает новые возможности для больных сахарным диабетом 2-го типа относительно оптимизации гликемического контроля и качества жизни., Огляд присвячений новій формі пероральних антидіабетичних препаратів із фіксованою дозою — комбінації метформіну сповільненого вивільнення та глімепіриду. Амарил®М СР (2/500 мг) — нова лікарська форма, що забезпечує швидке вивільнення глімепіриду, а потім повільне вивільнення метформіну з мультиполімерного гідрофільного матриксу незалежно від рН. На підставі дослідження терапевтичної ефективності та біодоступності показано, що ця форма характеризується оптимальною фармакокінетикою метформіну та глімепіриду, не призводить до збільшення частоти гіпоглікемій, може призначатися одноразово на добу й асоційована з меншою вираженістю шлунково-кишкових побічних ефектів, а також із більшою прихильністю до лікування. Застосування Амарилу®М СР створює нові можливості для хворих на цукровий діабет 2-го типу щодо оптимізації глікемічного контролю та якості життя.

Purpose Three continuous dosing strategies of cisatracurium (CIS) for acute respiratory distress syndrome (ARDS) have been described in the literature. After implementation of a ventilator synchrony protocol (VSP), we sought to determine which continuous CIS dosing strategy utilized the least amount of drug without compromising efficacy. Methods We retrospectively reviewed patients with ARDS receiving continuous CIS from January 1, 2013 to December 31, 2018. We categorized patients into one of three dosing strategies: fixed dose (FD), titration based solely on train-of-four (TOF), or the VSP. We documented drug consumption and determined efficacy by comparing the change in PaO2/FiO2 ratio (P/F) and oxygenation index (OI) from baseline up to 48 h. Results A total of 1047 patients were screened, and 189 met inclusion criteria (VSP = 69, TOF = 99, FD = 21). Drug consumption (mg) was significantly lower in the VSP arm: 415 [IQR 318–528] compared to both the TOF: 665 [IQR 472–927] and the FD arms: 1730 [IQR 1695–1800], p < 0.001 for each. The change in P/F and OI from baseline were statistically equivalent at all time points. Conclusion Without impacting efficacy of gas exchange, a protocol using ventilator synchrony for CIS titration required significantly less drug compared to TOF-based titration and a fixed dosing regimen.

The aim of the study was to evaluate the safety of the use of organotin compounds containing a fragment of 2,6-di-tert-butylphenol as pharmaceutical substances when administered intragastrically to Wistar outbred rats (females). Material and methods. The objects of the study were three organotin compounds: ((3,5-di-tertbutyl-4-hydroxyphenylthiolate) triphenyltin (Me-5), (3,5-di-tert-butyl-4-hydroxyphenylthiolate)trimethyltin (Me-4), bis(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (Me-3). Acute toxicity study were performed on 106 Wistar rats (female) weighing 190-210 g by "fixed dose" and "up and down" methods according to the OECD protocols. Results. According to the harmonized system of hazard classification and labeling of chemical products (GHS) the studied organotin compounds should be assigned to the following toxicity classes: Me-5 — IV, Me-3 — V, Me-4 — II. Average lethal dose in intragastric administration for Me-5 is LD50 = 955.0 ± 58.3 mg/kg, the value of LD50 for Me-3 is conventionally assumed to be much more than 2000 mg/kg, for Me-4 is in the range of 5 to 50 mg/kg. Discussion. The modification of tin-organic molecules in the course of directed synthesis opens broad prospects for the creation of a new class of anticancer drugs. In the course of the experimental study, the regularities of the "structure-toxicity" relationship of organic tin derivatives were revealed: the introduction of the 2,6-di-tert-butylphenol group significantly reduces toxicity compared to the corresponding initial substances; methyl derivatives are more toxic than their phenyl analogues. Compounds of GHS toxicity classes IV and V can be considered as leading candidates for promising preclinical studies in the field of experimental oncology. Conclusion. Substances of Me-3 and Me-5, which have the highest safety for intragastric use, were recommended for further study as antitumor drug agents.

Objectives: We analyzed patient-reported sleep parameters for an extended-release methylphenidate formulation (PRC-063) in adolescents with attention-deficit/hyperactivity disorder. Methods: Clinic...

Objective Gynaecological cancer surgery is associated with high rates of venous thromboembolism (VTE) despite recommended prophylaxis. We sought to investigate the impact of extended prophylaxis with fixed dose and weight based LMWH in patients undergoing gynaecological cancer surgery. Methods VTE rates were recorded in patients who received LMWH prophylaxis (4500 IU Tinzaparin once daily) for the duration of hospital stay (2006–2012) (n = 610) and were compared with VTE rates in patients who underwent surgery after the introduction of extended prophylaxis (3500/4500 IU Tinzaparin for patients with BMI 40 kg/m2) (2012–2017) (n = 651). Peak (4 h) anti-Xa levels in a subset of patients were also evaluated. Results 73 (5.7%) cases of VTE were recorded during 1 year of follow-up. 20 cases occurred during hospital stay. There was no significant difference in the rate of VTE between the extended prophylaxis cohort and the standard prophylaxis cohort. 23/24 patients who developed VTE in the extended prophylaxis cohort received a fixed (4500 units) dose of Tinzaparin. 63% of patients who received a fixed LMWH dose had peak anti-Xa levels below the target range (0.2–0.4 IU/ml). Peak anti-Xa was lower in patients who subsequently developed VTE compared with those who received either fixed dose (P = 0.041) and weight adjusted Tinzaparin (P = 0.0006). Conclusions Extended prophylaxis with Tinzaparin does not significantly reduce VTE rates in gynaecological cancer patients post surgery. Peak anti-Xa levels may be suboptimal in many patients receiving a fixed LMWH dose. Further studies are required to determine whether weight adjusted doses of Tinzaparin may provide more effective prophylaxis following gynaecological cancer surgery.

New liquid chromatographic technique was established for the simultaneous estimation of tinidazole, omeprazole and amoxicillin in the fixed dose combination (HP-KIT by Sun Pharma). RP-HPLC elution has performed by using the Phenomenex Luna column (250 mm x 4.6 mm) having internal diameter and the packing material of size 5µm) in isocratic mobile phase of solution A: acetonitrile at a ratio of 80:20 v/v (Solution A consists of Buffer: Acetonitrile: Methanol: Triethylamine in the ratios of 68:22:10:0.01 respectively). The selected flow rate was kept as 1 ml/min and selected wavelength was 230 nm was for detection of the drugs in UV detector. As per the ICH guidelines, the method validation was carried out. Moreover, the different parameters of method such as precision, specificity, linearity, robustness and accuracy were established. The time of retention for the tinidazole, amoxicillin, and omeprazole were 4.021 2.324, and 7.332 minutes respectively. The RP-HPLC approach was robust and accurate, so it is appropriate for repetitive assay of drugs and quality control. This method is effectively used for the assessment of marketable dosage form preparation. Keywords: RP-HPLC, Amoxicillin, Tinidazole, Omeprazole, Method Development, Method Validation.

Background: Foslevodopa/foscarbidopa, formerly known as ABBV-951, is a formulation of levodopa/carbidopa prodrugs with solubility that allows for subcutaneous (SC) infusion and is in development for the treatment of motor complications for patients with advanced Parkinson’s disease (aPD). Objective: The current work characterizes the levodopa (LD) and carbidopa (CD) pharmacokinetics (PK) following SC infusions of foslevodopa/foscarbidopa delivered at four different infusion rates in PD patients. Methods: This was a Phase 1, single ascending dose, single-blind study conducted in 28 adult male and female subjects at seven sites in the United States. Foslevodopa/foscarbidopa was administered via abdominal SC infusion in PD patients over 72 hours. Patients were stratified in 4 groups and received a fixed dose of foslevodopa/foscarbidopa based on their oral daily LD intake. Serial plasma PK samples were collected to assay for LD and CD concentrations. Safety and tolerability were assessed throughout the study. Results: LD exposure quickly reached steady state and remained stable with minimal fluctuations. Foslevodopa/foscarbidopa infusion provides stable LD and CD exposures compared to oral LD/CD dosing with the average steady-state exposure ranging from 747-4660 ng/mL for the different groups. Conclusion: Foslevodopa/foscarbidopa was able to provide stable LD and CD exposures in PD patients over 72 hours via SC route of delivery with very low fluctuation in LD concentration level across a wide range of clinically relevant exposures. Foslevodopa/foscarbidopa had a favorable safety profile. The low PK fluctuation following foslevodopa/foscarbidopa infusion is expected to maintain LD exposure to treat aPD patients within a narrow therapeutic window.

To compare the ventilatory and clinical outcomes associated with a fixed-dose cisatracurium infusion versus a titrated infusion strategy in patients with Acute Respiratory Distress Syndrome (ARDS).Single-center, retrospective, cohort study in a medical ICU of a tertiary care academic medical center. Adult patients ≥18 years old with a continuous infusion of cisatracurium for ≥12 h for treatment of ARDS were included. The primary outcome was the PaO2 /FiO2 ratio assessed at 24 and 48 h following cisatracurium initiation. Secondary outcomes included amount of average dose of drug administered, 28-day ventilator-free days, LOS, and hospital mortality.167 patients were included; median baseline PaO2/FiO2 was 97 (76-146), median SOFA score of 9 (7-11), and ICU mortality was 71/167 (43%). In a mixed-effects model, fixed dose and titrated cisatracurium associated with similar changes in PaO2/FiO2 assessed at 24 and 48 h (p = 0.316). Fixed-dose was associated with a3-fold increase in drug exposure (average dose 6.4 (5.4-8.0) vs. 2.0 (1.5-2.8) mcg/kg/min; p0.001, respectively). No differences were observed in secondary clinical endpoints.Fixed-dose cisatracurium was associated with similar ventilatory and clinical outcomes compared to titrated strategy, yet it was associated with a 3-fold increase in dose administered.

The effective treatment of asthma is important in terms of improving the quality of life and decreasing the number of hospital admissions due to acute exacerbations. Parasymphatic activity is increased in patients with asthma. This is one of most important part of airway obstruction which has a great potential for reversibility. The evidence about the synergic interaction between inhaled corticosteroids (ICS), long acting beta-2 agonists (LABA), and long acting muscarinic antagonists (LAMA) encourages the use of LAMA in asthma. Tiotropium treatment was found to be successful in patients with recurrent exacerbations in whom asthma was uncontrolled despite treatment with other add on treatments that were recommended at GINA step 4. These findings triggered several clinical studies on fixed dose ICS/LABA/LAMA for asthma treatment. Three studies that have been published recently showed that fixed dose ICS/LABA/LAMA improved the lung functions and decreased the exacerbation rate without increasing the dose of ICS or LABA in asthma. In this review, the mechanisms of action of LAMA in asthma were summarized and possible role of fixed dose ICS/LABA/ LAMA in asthma treatment was discussed under the light of current literature.

Aim: The present research work was carried out to formulate stable fixed dose combination tablets of Bilastine and Montelukast Sodium, used to treat allergic rhinitis associated with asthma and rhino-conjunctivitis on basis of pre and post post-compression parameters evaluation and drug-drug-excipients compatibility studies. Methods: Direct compression methodology was used for tablet production and final composition of drugs and excipients was optimized by evaluating pre and post compression evaluations of blend and tablets respectively. The chemical instability and stability studies were carried out using HPLC method. Results: The Evaluation of pre-compression parameters of batch F1 to F5 shows that as we increase the amount of sodium starch glycolate and colloidal silicon dioxide from F1 to F5, bulk density and tapped density increases slightly whereas the compressibility index and hausner’s ratio of tablets was shifted from excellent to good. Angle of repose shows excellent flow property from F3-F5. After evaluation of post-compression parameters from F1 to F5, there is no significant difference in diameter, thickness and average weight of tablets. The hardness of tablets was decreased slightly from F1 to F5 therefore, the % friability was found to be increased from F1 to F5 and disintegration time was found to be decreased from F1 to F5. Dissolution studies shows % release of Bilastine and Montelukast was increased towards F1 to F5 as the percentage of Sodium Starch Glycolate increases. The drug-drug-excipients compatibility shows that there is no physical and chemical incompatibility between the drug-drug-excipients at accelerated conditions. The stability studies show that % assay of long term and accelerated samples are within 100±2%. Conclusion: The optimized composition found in order to scale up the production of tablets.

BACKGROUND Rasburicase (recombinant urate oxidase) has been proven to be an effective therapy for prevention of tumour lysis syndrome (TLS). The recommended daily dosing regimen of rasburicase is 0.2 mg/kg/day for 5 days which is expensive and unaffordable to many patients in the developing countries. The purpose of the present study was to evaluate the effect of single 1.5 mg dose rasburicase in the management of tumour lysis syndrome. METHODS This is a follow-up study done at our institute. Fifty (50) patients with tumour lysis syndrome who received rasburicase from August 2015 to January 2020 were enrolled in this study RESULTS Single dose of rasburicase is effective in decreasing serum uric acid level in significant number (N = 41) of patients. Percentage of patients having uric acid less than 7 mg after single dose of rasburicase in 48 hours - 82.9 % (N = 34) while 17 % (N = 7) were found to have uric acid levels of more than 7 mg/dl. The percentage of patients with uric acid levels more than 7 mg/dl reduced from 36.5 % after 24 hours to 17 % after 48 hours. This indicates that the uric acid levels show a declining trend even after 24 hours without giving an additional dose of rasburicase. There was no relationship between uric acid levels at 24 hours and percentage change in creatinine level from baseline to 24 hours (correlation coefficient (r) = -0.047, P = 0.770. Patients who required additional dose (N = 9) had high base line value of uric acid and their high value was maintained over the follow up period of three days. Patients with pre exiting kidney disease and high level of baseline uric acid also needed dialysis (N = 3). CONCLUSIONS In majority of patients, a single 1.5 mg dose of rasburicase is an effective way to reduce raised uric acid in appropriate circumstances. KEYWORDS Single Dose, Recombinant Urate Oxidase, Uric Acid, Leukemia, Tumour Lysis Syndrome, Rasburicase

The aim of the current study work was to formulate and assess a fixed dose mixture tablet of instant release oral solid dosage form comprising two anti-diabetic drugs (linagliptin and metformin hydrochloride) for managing of diabetes mellitus type 2.The innovator drug product (Jentadueto Tablet) was evaluated for the various evaluation parameters, which have been taken into consideration during the drug product development. Pre-formulation evaluation was accomplished to safeguard better parameters of formulated drug product. On the result of pre-formulation evaluation and innovator drug product characterization, the model drug product was recognized in various steps. The established formulation was augmented for different excipients. The instant release film covered tablet of linagliptin and metformin HCl was expressed and augmented at laboratory scale. The individual steps (procedures) were improved for the same and the scale-up contemplation have been engaged into account certify the product performance at pilot plant-up to commercial scale-up. Keywords: anti-diabetic, linagliptin, metformin

RATIONALE: Reducing nicotine content in cigarettes to ≤ 2.4 mg per g of tobacco [mg/g] reduces smoking behavior and toxicant exposure among adult daily smokers. However, cigarettes with similar nicotine content could support continued experimentation and smoking progression among young adults who smoke infrequently. OBJECTIVES: This study evaluated the threshold for nicotine in cigarettes that produces reactions associated with smoking progression in a sample of young adults who smoke infrequently. METHODS: Young adults (n=87, 18-25 years, 49% female) using tobacco products ≤15 days per month completed three counterbalanced, double-blinded sessions, each measuring Positive and Negative subjective reactions to fixed doses of smoke from investigational cigarettes containing one of three different nicotine contents: normal (NNC; 15.8 mg/g); very low (VLNC; 0.4 mg/g); and intermediate (INC; 2.4 mg/g). In a final session, participants chose one of the cigarettes to self-administer. RESULTS: Post-cigarette breath carbon monoxide was greater for VLNC than for NNC (p

Objective. The aim of this study was to understand whether enhanced CT can provide more information than unenhanced CT on diagnosis of sarcopenia. Materials and Methods. We reviewed the enhanced CT data of 45 patients of pancreatic cancer. Manual tracing of the psoas muscles was used for measuring the cross-sectional muscle areas and attenuation at umbilicus level; afterwards, PMI, PMD, and Δ PMD were calculated. Results. In the unenhanced scanning, arterial, venous, and parenchymal phases of enhanced CT, PMI values were 6.905 ± 2.170, 6.886 ± 2.195, 6.923 ± 2.239, and 6.866 ± 2.218, respectively, and the difference was not statistically significant. The PMD values at different phases were 34.311 ± 7.535, 37.487 ± 7.118, 40.689 ± 7.116, and 42.989 ± 7.745, respectively, which were gradually increased, and the difference was statistically significant. Meanwhile, the PMD of arterial phase, venous phase, and parenchyma phase showed a linear correlation with PMD of unenhanced scanning phase. 31 patients had low PMD and 14 had normal PMD during the unenhanced scanning phase. With the addition of contrast agent, ΔPMD values increased faster in the low PMD group than in the normal PMD group during the venous and parenchymal phases (7.048 ± 3.067 vs 4.893 ± 2.558; 9.581 ± 3.033 vs 6.679 ± 2.621; p < 0.05 ), which made the gap between PMD after contrast-enhancement vs. unenhanced scanning smaller. Conclusion. The use of contrast agent has no effect on the manually measured PMI values but can change the results of PMD. This change makes the difference of PMD in different enhancement phases smaller than that in plain scan phase and furthermore increases the examination cost; therefore, it is not recommended to use enhanced CT routinely with fixed dose administration of contrast agent for patients’ assessment of PMI and PMD.

In this study, acute toxicity of kenikir leaf (Cosmos caudatus HBK) ethanolic extract was conducted on Wistar white male rats with fixed dose procedure. The extraction method used was maceration using 70% ethanol. A dose of 2000 mg/kgBW was determined as the starting dose based on the preliminary test result. The rats used in the main test were divided into the normal group and the 2000 mg/kgBW dose group, each used five animals in each group. The results of the test showed that there were no deaths or toxic symptoms both of the normal group and the 2000 mg/kgBW dose group. The conducted preliminary test results a dose of 2000 mg/kgBW as the starting dose. Next, main test is done toward two groups of rats: Normal group and 2000 mg/kgBW dose group each consist of five animals. The main test results in neither deaths nor toxic symptoms from those groups. The range of toxic doses of kenikir leaf ethanolic extract that can cause acute toxicity is >2000 mg/kgBW, and hence, this experiment classified in the practically nontoxic category. Statistical analysis on effect to macroscopic organs of the liver, heart, and kidney showed no significance (P > 0.05) from kenikir leaf ethanolic extract. Average levels of biochemical parameters from the 2000 mg/kgBW group and the normal group were in the normal range. Ethanolic extract at a dose of 333 mg/kg BW does not cause severe pancreatic damage, and hence, it is considered safe for use as an antidiabetic.

Cemiplimab, a human monoclonal antibody targeting programmed cell death-1 (PD-1) receptor, demonstrated antitumor activity in patients with advanced malignancies and a safety profile comparable to other anti–PD-1 therapies. This population pharmacokinetics (PopPK) analysis of cemiplimab included 11,178 pharmacokinetics (PK) observations from 548 patients pooled from a first-in-human study (Study 1423; NCT02383212) in advanced malignancies and a Phase 2 study (Study 1540; NCT02760498) in advanced cutaneous squamous cell carcinoma (CSCC). Most patients (80.3%) received cemiplimab 3 mg/kg every 2 weeks (Q2W) intravenously (IV). A PopPK model was developed by evaluating two-compartment linear models with an empirical non-linear function describing time-varying change in cemiplimab clearance and covariates that improved goodness-of-fit. PopPK simulations were used to describe cemiplimab exposure generated by a fixed 350 mg every 3 weeks (Q3W) IV dose regimen. PopPK modeling showed that a two-compartment model with zero-order IV infusion rate and first-order elimination rate well described individual concentrations of cemiplimab. Although several covariates, including baseline body weight and albumin concentrations, had a modest impact on cemiplimab exposure, the magnitude of influence was within the typical observed PK variability of approximately 30%. Based on PopPK simulation results, the 350 mg Q3W dose regimen was selected for further studies in advanced malignancies, including advanced CSCC. Similarity in observed cemiplimab exposure at the fixed 350 mg Q3W and the weight-based 3 mg/kg Q2W dose regimens confirmed this fixed dose selection. A robust PopPK model was developed to describe cemiplimab concentrations and supported use of the fixed 350 mg Q3W IV dose regimen. Supplementary Information The online version of this article (10.1007/s10928-021-09739-y) contains supplementary material, which is available to authorized users.

In order to improve the effectiveness of antihypertensive treatment, doctors more often prescribe fixed dose combinations of two or three antihypertensive products. In this case, the concomitant effects of these products contribute to better control of blood pressure, improve patient’s adherence to treatment and reduce the risk of side effects. The fixed dose combination of lercanidipine and enalapril is quite new for Ukrainian physicians; however, there is already a sufficient evidence base for the efficacy and safety of such combination therapy. Lecranidipine – enalapril combination reduce systolic and diastolic blood pressure in patients with moderate hypertension without severe side effects. In addition, this combination is effective and safe in patients with comorbidities.

Objective: The objective of the study was to analyze the nonsteroidal anti-inflammatory drugs (NSAIDs) and respiratory fixed-dose combinations (FDCs) recently banned in India. Methods: This observational study was conducted at the Department of Pharmacology, B. J. Medical College, Ahmedabad, Gujarat. The data were collected from the report on the banned FDCs submitted by the drug technical advisory board subcommittee. Total 195 FDCs belonging to NSAIDs (33) and respiratory group (162) were assessed for class, number of active pharmacological ingredients, formulations, indications, and reasons for banning. Results: The mean number of drugs in FDCs of NSAIDs was 2.6, while in respiratory FDCs, it was 3.6. The most common NSAID formulation was uncoated tablet (15, 30%) while it was syrup in respiratory (49, 30%). The most common reasons for banning these FDCs were safety concerns (153, 78.4%), followed by mismatched pharmacodynamics in respiratory FDCs and mismatched pharmacokinetics in NSAIDs FDCs. The NSAIDs FDCs were marketed for pain (70%) while respiratory FDCs were marketed for cough and cold (62%). Most common NSAIDs FDCs contained NSAID with NSAID (18%), while in respiratory FDCs combinations of a cough suppressant, expectorant, and soothing agents (10%) were present. Conclusion: Evaluation of FDCs is essential to prevent the marketing of irrational FDCs.

Objective: To explore the prokinetic effect of Ranitidine, to compare it with the prokinetic effect of Neostigmineand to observe the potentiating prokinetic effect of Ranitidine and Neostigmine in combination. Study Design: Randomised controlled trial (experimental study). Place and Duration of Study: Multi disciplinary centre, Army Medical College, Rawalpindi, from Jan to Dec 2015. Methodology: Experiments were performed on three groups of rabbits (n=6) and Cumulative dose responsecurves were plotted using isolated duodenal tissue on power lab (USA). In the first two groups of experiments,cumulative concentrations of Neostigmine and Ranitidine were studied separately with neostigmine acting as acontrol and in the third group the potentiating effect of a fixed dose of ranitidine on neostigmine was evaluated. Results: Neostigmine’s response was taken as 100 percent and Ranitidine’s response when compared to it came out to be 197 percent. The dose response curve of Neostigmine was shifted to the left and upwards in the presence of Ranitidine. The percent response with Neostigmine alone was taken as 100 percent and increased to 212 percent when the tissue was pre-treated with Ranitidine. Conclusion: Our study has indicated that Ranitidine has marked prokinetic effect which is found to be greaterthan Neostigmine. It is also inferred that Ranitidine can potentiate the prokinetic effect of Neostigmine.

WHAT IS KNOWN AND OBJECTIVE Therapeutic alternatives to simplify antiretroviral therapy (ART) in HIV-infected children are needed. We report our experience with abacavir(ABC)/lamivudine(3TC) individualized dose compounded capsules (IDCC). COMMENT We present a prospective case series of HIV-infected children who did not weigh enough to receive the adult fixed-dose combination including ABC/3TC 600mg/300mg, and were treated with weight-adapted ABC/3TC IDCC in Barcelona, Spain. Thirteen patients (12 girls) received ABC/3TC IDCC for a median(IQR) time of 30(17-54) months. No significant changes were observed in CD4 cell counts, weight or height z-scores over time. Suppression of viral replication was maintained in 7 patients with undetectable viremia at baseline. Another 5 patients achieved viral suppression with ABC/3TC IDCC-based ART, while one non-adherent girl did not. No adverse events related to ABC/3TC IDCC were observed. WHAT IS NEW AND CONCLUSION Despite small numbers, the long-term use of ABC/3TC IDCC was feasible, safe, and effective in the treatment of HIV-infected children.

Mebendazole (Anthelmintic) in combination with Quinfamide (Luminal Amebicide) is extensively used for treatment of Helminthiasis and Amoebiasis. Till present, there is no work found on development of a single combine UPLC method for determination mebendazole and quinfamide with their relative impurities and antioxidants in Fixed dose combination (FDC). The present work describes use of a statistical quality by design approach to develop a robust, stability Indicating, cost-effective and time saving method for simultaneous determination of both APIs with their related impurities and antioxidants by UPLC. Using phase wise screening approach, the final chromatographic conditions employed a Waters Cortecs UPLC C18, 150 mm × 2.1 mm, 1.6 μm column with mobile phase consisting of 0.025% Trifluoracetic acid and Acetonitrile/methanol (90:10) in a gradient program. The flow rate and injection volumes were 0.38 mL/min & 2 μl, respectively, and detection was done at 260 nm. The method was validated according to ICH and ANVISA guidelines. The results evidently reflect that the QbD Approach concept can be effectively applied to develop analytical methods for Fixed dose combinations with fewer trials and error-free experimentation.

Introduction The phase 2 POPLAR and phase 3 OAK studies of the anti–programmed death-ligand 1 (PD-L1) immunotherapy atezolizumab in patients with previously treated advanced NSCLC revealed significant improvements in survival versus docetaxel (p = 0.04 and 0.0003, respectively). Longer follow-up permits evaluation of continued benefit of atezolizumab. This study reports the final overall survival (OS) and safety findings from both trials. Methods POPLAR randomized 287 patients (atezolizumab, 144; docetaxel, 143) and OAK randomized 1225 patients (atezolizumab, 613; docetaxel, 612). The patients received atezolizumab (1200 mg fixed dose) or docetaxel (75 mg/m2) every 3 weeks. Efficacy and safety outcomes were evaluated. Results A longer OS was observed in patients receiving atezolizumab versus docetaxel in POPLAR (median OS = 12.6 mo versus 9.7 mo; hazard ratio = 0.76, 95% confidence interval [CI]: 0.58–1.00) and OAK (median OS = 13.3 versus 9.8 mo; hazard ratio = 0.78, 95% CI: 0.68–0.89). The 4-year OS rates in POPLAR were 14.8% (8.7–20.8) and 8.1% (3.2–13.0) and those in OAK were 15.5% (12.4–18.7) and 8.7% (6.2–11.3) for atezolizumab and docetaxel, respectively. Atezolizumab had improved OS benefit compared with docetaxel across all PD-L1 expression and histology groups. Most 4-year survivors in the docetaxel arms received subsequent immunotherapy (POPLAR, 50%; OAK, 65%). Of the 4-year survivors, most had Eastern Cooperative Oncology Group performance status of 0 and nonsquamous histological classification and approximately half were responders (POPLAR: atezolizumab, seven of 15; docetaxel, three of four; OAK: atezolizumab, 24 of 43; docetaxel, 11 of 26). Treatment-related grade 3/4 adverse events occurred in 27% and 16% of atezolizumab 4-year survivors in POPLAR and OAK, respectively. Conclusions Long-term follow-up suggests a consistent survival benefit with atezolizumab versus docetaxel in patients with previously treated NSCLC regardless of PD-L1 expression, histology, or subsequent immunotherapy. Atezolizumab had no new safety signals, and the safety profile was similar to that in previous studies.

Objective: Migraine headaches are one of the most common and debilitating diseases. Chronic migraine (CM) is a type of migraine that reduces quality of life and causes disability. Botulinum toxin A (BT-A) was approved in 2010 by the Food and Drug Administration for CM as one of the treatment options. In BT-A treatment, follow the pain (FTP), fixed-site fixed-dose (FSFD) methods, and combined injections are prevalent. This clinical trial aimed to compare the effects of two methods of BT-A injections in patients with CM to determine the method with the fewest complications, the strongest therapeutic effects, and the lowest costs in improving quality of life. Materials and Methods: In this preliminary clinical trial, 40 patients with CM were screened, and after examining the inclusion criteria, 18 patients completed the trial. After a baseline examination and experiencing a 28-day baseline period, they were randomly divided into FSFD and FTP groups. In our study, we used the Quality of Life Questionnaire, the Migraine Daily Note, and Headache Impact Test-6. Results: A total of 17 women and 1 man completed the trial. Severity and rate of headaches and quality of life scores had better changes in the following months with similar trends in both groups without a significant difference. Conclusion: The comparison of the scores showed an improvement in most patients, but there was no significant difference between the FSFD and FTP groups. However, the results indicated a greater response to the treatment and a higher rate of drug use in the FSFD group.

The combination of Canagliflozin and Metformin was available as fixed dose tablets for the treatment of type 2 diabetes. The present method aims to develop a simple, precise and accurate spectrophotometric method for simultaneous determination of Canagliflozin and Metformin in commercial formulation. The method utilizes Vierordt’s equation based on the measurement at two wavelengths 290nm (?max of Canagliflozin) and 236nm (?max of Metformin). The method exhibited linear range of 2.5 to 15µg/ml and 5 to 17.5µg/ml for Canagliflozin and Metformin, respectively, with a correlation coefficient of 0.999. The LOD and LOQ for Canagliflozin were found to be 0.43 and 1.31 respectively. For Metformin the LOD and LOQ were found to be 0.49 and 1.49 respectively. The recovery of Canagliflozin and Metformin were found to be 99.43 and 98.82 respectively. The results were validated statistically as per ICH guidelines and were found to be satisfactory. To conclude, the developed UV spectrophotometric method is more economical for analysis of Canagliflozin and Metformin in both bulk and pharmaceutical dosage form for routine analysis. Keywords: Canagliflozin, Metformin, Vierordt’s equation, UV-Spectrophotometry, ICH guidelines

Self-medication is widely practiced everywhere in the world. The drug for self medication has proven efficacy and safety for short-term use in minor illnesses but there is the potential for misuse and abuse of them. A cross sectional survey was conducted by visiting 800 houses of Anand district of Gujarat. The details regarding self medication were inquired which include the medical conditions for which they used, availability of Fixed Dose Combinations (FDCs), previously prescribed medicines taken as self medication, sources, reference & reasons for self medication. The Knowledge of the study participants regarding Self medication was inquired by revealing the history of illness in past six months. Ethics Committee approval was taken prior to the study. A total of 501 without prescription medicine formulations were found in 245 (30.63%) houses, more in the urban area (38.25%) than the rural (23%). The common conditions for self medication were body ache, arthritis and fever (36.53%). The commonest source was pharmacy stores whereas family, friends or relatives were commonest sources of information for self medication. The Self decision was taken for 32.93% of medicines. Total 43 medicines prescribed earlier were used as self medication for other family member including 12 preparations for pediatric use. Only 126 participants had 222 illness episodes in past six month. Of them 18 study respondents self medicated. Half of the respondents were having the knowledge regarding medicine. There is a need of emphasizing on proper awareness and education related to self-medication. Keywords: Self-medication, Medicines without prescription, Rural, Urban.

Fasika Berhanu Tola,1 Gizachew Tilahun Anbessa,2 Berhan Begashaw Yikna3 1Curative and Rehabilitative Core Process Section, Dire Dawa City Administrative Health Bureau, Dire Dawa, Ethiopia; 2School of Pharmacy, Faculty of Health Science, Jimma University, Jimma, Ethiopia; 3Department of Pharmacy, College of Health Science, Debre Berhan University, Debre Berhan, EthiopiaCorrespondence: Berhan Begashaw Yikna Tel +251-919-365-179Email berhan.uog1912@gmail.comBackground: Health facilities (HFs) need extensive ranges of anti-tuberculosis (TB) drugs and related TB laboratory commodities (LCs) for diagnosis, prevention, and treatment of TB and multi-drug-resistance (MDR)-TB. This study was aimed to assess anti-TB commodities management performance at public HFs of Dire Dawa city administration, Ethiopia.Methods: A cross-sectional study design in 16 HFs providing TB and MDR-TB related service using quantitative and qualitative method was conducted. Semi-structured questionnaires and observation checklists with logistic indicators assessment tools were used to collect data. We used an in-depth interview and analyzed using a thematic approach. Quantitative data were entered into Epi-Data version 3.1 and transported to SPSS version 20 to analyze the results. Chi-square was used to test the association and a P-value< 0.05 was statistically significant.Results: The majority(13; 81.3%) of HFs used a health commodity management information system. Forty-two (40%) bin cards (BCs) for first line anti-TB drugs were not updated, while 62.5% of BCs were updated for second line drugs. On average, 43% of HFs accurately reported a report and requisition format (RRF) had significant association with the presence of a logistic management information system (LMIS) and standard operating procedure (P=0.019). Of the HFs, 50% had good storage conditions and guidelines (P=0.041). Regimen change (56.3%; P=0.035), receive near expiry (56.3%; P=0.035), and defective practice to first expired-first-out (50%; P=0.007) were reasons for wastages. About 50% and 66.6% of HFs were stocked out for isoniazid 300 mg, rifampicin, isoniazid, pyrazinamide (RHZ fixed dose), and ethambutol 400 mg with a mean stock out duration of 10.8, 18.9, and 70.5 days, respectively. Regimen change (68.8%; P=0.026), low demand (56.3%; P=0.041), and delay to resupply (37.5%; P=0.041) were reasons for stock out of anti-TB commodities.Conclusion: Anti-TB drugs and LCs management performance of the HFs were found to be defective, which was confirmed by unsatisfactory data records, inconstant reports, deprived stock record accuracy, long lead time, high stock out rate, wastages, defective storage conditions, lack of training, and management support. Hence, respective organizations should improve their responsible activities to secure an uninterrupted supply of anti-TB drugs and LCs.Keywords: anti-TB drugs, MDR-TB, laboratory commodities, health facilities, Ethiopia

Fixed dose combinations of ezetimibe and rosuvastatin are well known to provide significantly superior efficacy to rosuvastatin alone in lowering total cholesterol, and triglyceride levels. Therefore, in this recent work, we prepared fixed dose (10mg/10mg) ezetimibe and rosuvastatin tablet formulations, and a simple, selective and we established and validated rapid chromatographic method for the sensitive and simultaneous determination of rosuvastatin and ezetimibe. We performed the separation on Zorbax SB-C18 (100 mm x 4.6 mm, 3.5 µm particle size) column at 30 oC with a mobile phase that has a composition as water containing 0.1% H3PO4:methanol:acetonitrile (50:25:25 v/v/v) at 1.2 mL/min flow rate. We further performed validation studies according to ICH guidelines. Furthermore, we exposed rosuvastatin and ezetimibe to degradation conditions. We plotted peak area vs. concentration graphs for rosuvastatin and ezetimibe and used for defining the linearity of the detector response. In this suggested method, we observed linear relationships varying from 0.05 to 50 µg/mL for ezetimibe concentrations and from 0.05 to 25 µg/mL for rosuvastatin concentrations. We found the limit of detection values for rosuvastatin and ezetimibe as 0.006 and 0.008 µg/mL, respectively. Moreover, we further used the established method for to the analysis of ezetimibe and rosuvastatin from real spiked samples of rabbit serum.

Kasa (Cough) is one of the most frequent symptoms in pediatric age group for which parents look for medical care. It indicates that even after advancements in current medical science, cough is not being effectively controlled in children. With the above background, the present trial was aimed to study the efficacy of herbal tablet named as Shwasa Kasadi gutika in the management of Kasa. The objectives of the study were to assess the efficacy of trial drug on Kasa and its subjective and objective parameters.The study was a single group, single centre, fixed dose, interventional study. The subjective parameters were as per the clinical features of Kasa. Their grading was done as per their intensity. School going age group was more likely to suffer from the cough and male children were more in the study. There was significant improvement in all subjective criteria where as significant changes were noted in adventitious sounds and total leukocyte count. However, as it was conducted in limited samples, further large sample multi-centre studies would be preferable. Developing pharmaceutical standards of the tablet would also be a newer area of research.

A basic and specific HPLC-PDA (high-performance liquid chromatography-photodiode array) detector showing approach was created for the simultaneous estimation of anti-hypertensive medications—amlodipine besylate (AMD) and lisinopril (LIS). A successful chromatography method was developed using the SunFire C8 column (4.6 × 150 mm, 5 μm) with gradient elution of the mobile phase composed of 85:25 potassium dihydrogen phosphate in water and methanol at a flow rate of 0.7 mL/min. The wavelength was set at 212 nm for the simultaneous estimation of AMD and LIS. The retention time obtained was 5.1 and 10.5 minutes for AMD and LIS, respectively. Descriptive performance of the proposed HPLC methodology was measurably approved as for framework accuracy, linearity, robustness, specificity, precision, and forced degradation for identification and evaluation limits. The linearity range for AMD and LIS correlation coefficient value obtained was R2 andgt; 0.999. The drugs were exposed to forced degradation conditions—acidic, alkali, oxidation, etc. The newly developed reverse phase high performance liquid chromatography (RP-HPLC) method was applied for the detection of the referred to anti-hypertensive medications in their combination pharmaceutical tablets.

Cardiovascular diseases (CVD) are the world's leading cause of death. High blood pressure (BP) is the leading global risk factor for all‐cause preventable morbidity and mortality. Globally, only about 14% of patients achieve BP control to systolic BP 60%) require two or more drugs to achieve BP control, yet poor adherence to therapy is a major barrier to achieving this control. Fixed‐dose combinations (FDCs) of BP‐lowering drugs are one means to improve BP control through greater adherence and efficacy, with favorable safety and cost profiles. The authors present a review of the supporting data from a successful application to the World Health Organization (WHO) for the inclusion of FDCs of two BP‐lowering drugs on the 21st WHO Essential Medicines List. The authors discuss the efficacy and safety of FDCs of two BP‐lowering drugs for the management of hypertension in adults, relevant hypertension guideline recommendations, and the estimated cost of such therapies.

Our study aimed to identify the correlation between the presenting FT4 values and FT4 values after the radioiodine therapy. Patients, after 10 mCi fixed dose radioiodine therapy for thyrotoxicosis were followed up at 03, 06 months intervals at Nuclear Medicine, Peradeniya. The details on base line clinical presentation, FT4 levels and the clinical status after the radioiodine therapy were collected using an interviewer administered questionnaire. Data was analysed using the SPSS version 25 by using Pearson’s correlation and independent sample t-test. There were 70.2% of Graves’ disease patients and 29.8% of toxic multi nodular goitre patients among the 57 patients consented for the follow up. The Pearson’s correlation showed a weak relationship between the FT4 value on diagnosis and the FT4 value after 03 months (r=0.475, P0.003) and a moderate relationship between the presenting FT4 value and the FT4 value before any intervention on or before 06 months after the radioiodine therapy (r=0.644, P