A bioequivalence study comparing two formulations of lopinavir/ritonavir capsules.
This investigation was carried out to evaluate the bioavailability of a new single fixed-dose combination formulation of lopinavir and ritonavir, relative to reference product, Kaletra (133.3 mg lopinavir/33.3 mg ritonavir) capsules, manufactured by Abbott Laboratories, Chicago, IL, USA. The bioavailability study was carried out on 72 healthy male and female volunteers who received a single dose of 3 capsules (133.3 mg lopinavir/33.3 mg ritonavir) of the test (T) and the reference (R) products in the fasting state, in a randomized, balanced, 2-way crossover design. After dosing, serial blood samples were collected for a period of 72 hours. Plasma harvested from blood was analyzed for lopinavir and ritonavir by a sensitive and validated simultaneous liquid-chromatographic and mass-spectrometric (LC-MS/MS) assay. Mean oral clearance (Cl/F) values of the FDC were 4.92 and 23.54 l/h for lopinavir and ritonavir, respectively, the maximum plasma concentrations (C(max)), area under the plasma concentration-time curve up to the last measurable concentration (AUC(0-t)), and to infinity (AUC(0-infinity)), were analyzed statistically under the assumption of a multiplicative model. The time to maximum concentration (t(max)) was analyzed assuming an additive model. The parametric confidence intervals (90%) were calculated by Schuirmann's two 1-sided t-test criteria. It was found that the test/reference (T/R) ratios for the pharmacokinetic parameters AUC(0-t), AUC(0-infinity) and C(max) (after initial log transformation) were well within the bioequivalence acceptance range of 80-125% as per international regulatory guidelines. Therefore, the two formulations were considered to be bioequivalent [Food and Drug Administration 2003].
Tippabhotla
S K
SK
Department of Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Ltd., Udyog Vihar Industrial Area, Gurgaon, Haryana, India.
Thudi
N R
NR
Raghuvanshi
R
R
Khuroo
A H
AH
Gurule
S
S
Mishra
S
S
Monif
T
T
Lao
V K C
VK
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D061466:Lopinavir; D008297:Male; D013058:Mass Spectrometry; D011744:Pyrimidinones / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D002214:Capsules; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir