Comparative Single Dose Pharmacokinetics and Bioavailability Studies of Saquinavir, Ritonavir and their Optimized Cyclodextrin Complexes after Oral Administration into Rats using LC-MS/MS.

Abstract

Purpose: To compare pharmacokinetics and bioavailability of saquinavir (SQV) and ritonavir (RTV) and their optimized cyclodextrin complexes of anti-retro viral drugs after oral administration into rats.Methods: Rats were fasted overnight and dose equivalent to 10 mg/kg was administered orally via feeding tubes. Serial blood samples were collected, and plasma concentrations of both drugs and their complexes were determined using liquid chromatography tandem mass spectrometry, LCMS/MS.Results: After oral administration, half-life, apparent volume of distribution, total body clearance and bioavailabilities were calculated for both drugs and their optimized cyclodextrin complexes. The cyclodextrin complexes of both saquinavir (3860.93±138.50 ng.h/ml) and ritonavir (2300.19±118.21 ng.h/ml) had shown higher AUC0-∞ values compared to pure drugs, saquinavir (2293.04±82.13 ng.h/ml) and ritonavir (1636.07±162.51 ng.h/ml).Conclusion: Orally administered cyclodextrin complexes of SQV and RTV had shown higher bioavailabilities and higher peak plasma concentrations compared to SQV and RTV.

Keywords: Oral; LCMS/MS; Plasma; Bioavailability