ABSTRACT:
This paper is an attempt to compare the bioavailability of two Ivabradine tablet formulations (test and reference) containing 7.5mg mg of Ivabradine. The bioequivalence of two formulations (test and reference) was determined in 12 healthy Indian male volunteers (age: 25.25 +/- 4.69 years; weight: 60.50 +/- 5.04 kg) in An open label, balanced, analyst blind, randomized, two-treatment, two-period, two sequence, single dose, crossover study. Both formulations were administered orally as a single dose. Ivabradine plasma levels were determined by a validated LC-MS/MS method. The formulations were compared using the pharmacokinetic parameters peak plasma concentration (Cmax), time to reach maximum concentration (T(max)), area under the plasma concentration-time curve (AUC(0-t)), area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) and elimination half-life (t(1/2)) were 41.899 ± 18.7472 and 39.392 ± 10.5835 ng/mL, 1.229 ± 0.5786 and 0.958 ± 0.4626 h, 142.611 ± 57.3519 and 146.245 ± 52.9796 ng x hr/ml, 148.937 ± 57.2911and 153.723 ± 53.6352 ng x hr/ml, and 2.182 ± 0.3520 and 2.282 ± 0.4536 hr for the test and reference formulation, respectively. The 90% confidence intervals on the mean of the difference (test - reference) between log-transformed values of the two formulations were 88.40% to 117.32%, 85.13% to 109.74%, and 85.44% to 108.19% for C(max), AUC(0-t) and AUC(0-infinity) respectively. In conclusion, the test formulation is bioequivalent to the reference in terms of both the rate and extent of absorption. Both the formulations are well tolerated and no serious clinical adverse events causing death, disability, hospitalization, or dropouts of the subjects were encountered following a single dose administration of the investigational product.