A Bioequivalence Study of Carvedilol Tablets 12.5 mg in Healthy Human Subjects Under Fed Condition

Abstract

Aim & Objective: Carvedilol is a third-generation, nonselective β-blocker that also possesses α1- adrenergic blocking and antioxidants activity. Carvedilol is a multiple action oral antihypertensive drug. It is also used in left ventricular heart failure and CHF. This study was performed to compare the bioequivalence of a locally made oral tablet (test product) of carvedilol with the innovator’s product (reference product) by using data from plasma carvedilol concentration. Materials and Methods: Twelve healthy volunteers were selected after screening in the study that was of a randomized, open label, balanced, two treatment, two periods, two sequence, single dose, crossover design bioequivalence study, with a one week wash-out period. After an overnight fast, high fat high calories breakfast, which was started by subject 30 min before dosing and for at least 4 hrs post dose in each period. A single 12.5 mg carvedilol tablet of either the reference product or the test product was orally administered to each subject. A venous blood sample of five milliliters was drawn prior to dosing and at different time points intervals up to 48 hrs after dosing. LC/MS/MS was used to analyze the plasma sample for total carvedilol concentration. Results: The results showed that the maximum carvedilol concentration (Cmax) of all subjects found 29.25 ± 11.63 and 32.30 ± 16.75 ng/ml in reference and test product, respectively. Area under the plasma concentration-time profile curve from time zero to last time (AUC0-t) was 144.12 ± 41.95 and 160.38 ± 72.30 hr*ng/ml in reference and test product, respectively. Area under the plasma concentration-time profile curve from time zero to infinity time from observed (AUC0-inf (observed)) was 159.08 ± 49.30 and 167.08 ± 74.31 hr*ng/ml in reference and test product, respectively. Mean time to reach maximum plasma concentration (Tmax) was 2.34 ± 0.97 and 2.30 ± 1.00 hours in reference and test product, respectively. The 90% confidence interval (CI) for logarithm transformation data of the ratio geometric mean of Cmax, AUC0-last and AUC0-inf (observed) between these two treatments were 92.76-123.45, 92.65-120.11 and 88.15-114.49, respectively. The mean Cmax, AUC0-last and AUC0-inf (observed) between the two products were not statistically different.Conclusion: It can be concluded that the test product was bioequivalent to the reference product based on the criteria that the percent ratio of test parameters was within the range of 80.00-125.00 % with a 90 % level of confidence in terms of rate and extent of absorption. Carvedilol found to be well tolerated and no serious adverse events were found during study.