Bioequivalence Study of Two Fixed Dose Combination Tablet Formulations of Lopinavir and Ritonavir in Healthy Volunteers

Abstract

The study was designed to compare the rate and extent of absorption of two fixed dose combination tablet formulations of lopinavir (CAS 192725-17-0) and ritonavir (CAS 155213-67-5). This bioequivalence study was conducted using a standard preparation as reference and a generic alternative as test in 72 adult healthy volunteers within 18-45 years of age who received a single dose of the test or reference product under fasting conditions. A washout period of 10 d was maintained between period I and period II dosing. After dosing, blood samples were collected from 0 h (pre-dose) to 72 h postdose administration. Lopinavir and ritonavir were quantified using a validated LC-MS/MS method. The data obtained for each subject was evaluated for primary pharmacokinetic variables C(max), AUC(0-72), and AUC(0-Inf) with respect to % ratio and 90% confidence interval for log-transformed data. The 90% confidence intervals (obtained by analysis of variance, ANOVA) were well within the bioequivalence acceptance range of 80% to 125%. Thus, it can be concluded that the evaluated formulations are bioequivalent in terms of rate and extent of absorption. The safety profiles of both the test and reference formulations were comparable.

Influence of traditional Chinese medicines on the in vivo metabolism of lopinavir/ritonavir based on UHPLC-MS/MS analysis

“…The LLOQ was 25 ng/mL for lopinavir, which was markedly lower than 62.5 ng/mL [ 31 ] and 100 ng/mL [ 35 ] reported in the literature; and 5 ng/mL for ritonavir, which was lower than 12.5 ng/mL [ 31 ] and 99 ng/mL [ 36 ] reported in the literature. The RE values of lopinavir and ritonavir at the LLOQ were 3.45% and 1.46%, and the RSDs were 4.03% and 4.32%, respectively.…”

Access to unauthorized hepatitis C generics: Perception and knowledge of physicians, pharmacists, patients and non-healthcare professionals

“…[32] A bioequivalence study is usually conducted using a randomized, two-period, two-treatment, crossover design that allows comparison within individual healthy volunteers. [33] Hill and colleagues compared the bioequivalence of sofosbuvir and daclatasvir from seven pharmaceutical companies worldwide and concluded that they were all bioequivalent. [20] Finally, generic drugs must show label equivalence, which means that the indications are the same as the originator product.…”