Real-world clinical experience of ticagrelor in Indian patients with acute coronary syndrome after discharge from a tertiary setting

Background: To understand the usage pattern of ticagrelor in real-life clinical experience in Indian patients with the acute coronary syndrome (ACS) after discharge from a tertiary care setting. Methods: A retrospective multicentric observational study conducted across Indian healthcare centers having medical records of adult patients with ACS. Patients prescribed with ticagrelor post-discharge for at least 1 month were included. The study endpoints were to determine the clinical effectiveness of ticagrelor in post-ACS patients and adverse events reported during the study period. Results: A total of 1910 patients with ACS with a mean (SD) age of 58.2 (11.3) years were enrolled in this study. The median (IQR) duration of treatment was 30.0 (30.0-90.0) days. More than half of the patients (n=1115, 58.4%) were managed with interventional therapy. The most common comorbid conditions were type-2 diabetes mellitus (46.9%), followed by hypertension (36.8%). A total of 9.7% of patients reported complaints after treatment with ticagrelor. Among them, weakness, giddiness, and body pain were the most common (3.2%). Conclusions: This real-world study revealed that ticagrelor had been used widely in patients who underwent different management strategies. History of diabetes and hypertension were the most common risk factors. There were no major adverse events reported during the follow-up, indicating ticagrelor is well-tolerated in Indian patients with ACS.

Comparative bioavailability study of clonazepam after oral administration of two tablet formulations.

OBJECTIVE: To assess the bioavailability of clonazepam from two brands of 2 mg tablet formulations--Epitril and reference brand. METHODS: A two-way randomised cross-over bioavailability study was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of clonazepam by high performance liquid chromatography (HPLC) method. RESULTS: The mean Cmax, Tmax t1/2 beta and AUC (0-48) for Epitril were: 16.31 +/- 3.07 ng/mL, 1.63 +/- 0.48 h, 46.97 +/- 12.26 h and 207.70 +/- 57.07 ng/ml.h; for reference brand were 19.75 +/- 5.95 ng/mL, 1.42 +/- 0.29 h, 46.88 +/- 11.29 h and 215.70 +/- 50.89 ng/ml.h respectively. These were comparable and the differences were not statistically significant. CONCLUSION: Based on above pharmacokinetic parameters, Epitril was bioequivalent to reference brand.

Comparative bioavailability study of a conventional and two controlled release oral formulations of Tegretol (carbamazepine)--200 mg.

OBJECTIVES: To assess the bioquivalence of carbamazepine (CBZ) controlled release formulation A (Tegretol CR, local) vs formulation B (Tegretol CR, Basel) and confirm their controlled release characteristics by comparing with conventional formulation (Tegretol). METHODS: A three-way randomized cross-over bioavailability study was carried out using CBZ 200 mg tablets of conventional and two controlled release formulations in twelve healthy volunteers. Coded plasma samples were analysed for levels of CBZ by HPLC method. RESULTS: The mean Cmax, Tmax, t1/2 and AUC for formulation A were: 1.67 +/- 0.26 mcg/mL, 24 +/- 0 hr, 47.8 +/- 9.7 hr and 136.7 +/- 25.4 mcg/ml. h; for formulation B were 1.41 +/- 0.31 mcg/mL, 25 +/- 8 hr, 46.9 +/- 7.9 and 119 +/- 32.3 mcg/ml.h and for conventional formulation were 2.43 +/- 3.6 mcg/mL, 9.5 +/- 7.4 hr, 44.6 +/- 9.8 hr and 178.8 +/- 41.9 mcg/ml.h respectively. The fluctuation in plasma concentration within 24 h (peak:trough) were 11.7 +/- 8.14% with conventional formulation as compared to 0% and 1.2 +/- 3.98% with formulation A and B respectively. The mean Tmax for both the controlled release formulations was not statistically significant. On the basis of 90% confidence interval, mean AUC and Cmax values obtained after controlled release formulation A, though statistically significant (P < 0.05) lie well within the prescribed limits of 80-120% as compared to formulation B. Thus both the controlled release formulations were bioequivalent. In comparison to conventional formulation, both controlled release formulations gave lower Cmax, lower AUCs, higher Tmax values, less fluctuation in CBZ plasma concentrations, reduction in ratio of Cmax/AUC values, thus demonstrating controlled release characteristics of the formulation. CONCLUSIONS: Based on the above mentioned parameters both controlled release formulations are bioequivalent and demonstrate controlled release characteristics.

Comparison of absorption rate and bioavailability of two brands of carbamazepine.

OBJECTIVE: To assess the bioavailability of carbamazepine from two brands of carbamazepine--Tegretol 200 and Zen-200. METHODS: A two-way randomised cross-over bioavailability of carbamazepine was carried out in twelve healthy male volunteers. Coded plasma samples were analysed for levels of carbamazepine by high performance liquid chromatography (HPLC) method. Tegretol 200 and Zen-200 were tested for in-vitro dissolution profiles. RESULTS: The mean Cmax, Tmax and t1/2a for Tegretol 200 were: 2.17 +/- 0.42 mcg/mL, 11.67 +/- 6.37 h and 2.72 +/- 1.87 h; for Zen-200 were 3.10 +/- 0.05 mcg/mL, 3.50 +/- 2.11 h and 0.76 +/- 0.76 h respectively. These values were statistically significant. However AUC (0-96 h) value of 150.16 +/- 27.13 mcg/ml.h after Zen-200 was not statistically significant as compared to 128.68 +/- 20.22 mcg/ml.h after Tegretol 200. The in-vitro dissolution profiles of the two formulations were dissimilar. The fluctuations in CBZ levels after Tegretol 200 was significantly less as compared to Zen-200. The absorption profile as judged by parameter 'A' was 50.44 +/- 10.95 for Tegretol 200 and 42.49 +/- 18.89 for Zen-200. CONCLUSION: Based on parameter 'A' and other pharmacokinetic parameters, the marketed generic carbamazepine product, Zen-200 is not bioequivalent to Tegretol 200.

Determination of pyrazinamide in human by high performance liquid chromatography.

A facile and sensitive high performance liquid chromatographic (HPLC) technique has been developed for the determination pyrazinamide (PZA) in human plasma. Nicotinamide(NIA) is used as internal standard(IS). Plasma is deproteinized with 0.7 M perchloric acid; clear supernatant is neutralized with 1M NaOH and injected onto HPLC. The separation of pyrazinamide and the internal standard is carried out on a Supelco LC-18 (DB) column with a basic mobile phase. Pyrazinoic acid, the major metabolite, other anti-tuberculous drugs and endogenous components do not interfere with measurement of pyrazinamide. The limit of detection of pyrazinamide with this method is 0.2 mg/0.2 ml plasma (CV 8.2%).