Concomitant Administration of BILR 355/r with Emtricitabine/Tenofovir Disoproxil Fumarate Increases Exposure to Emtricitabine and Tenofovir: A Randomized, Open-Label, Prospective Study

Abstract

The objective of this study was to evaluate the pharmacokinetic interaction of ritonavir-boosted BILR 355 (BILR 355/r) with emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). This was an open-label, prospective study. For Group A, 26 healthy subjects were given FTC/TDF (200/300mg) once daily (QD) for 7days and then co-administered with BILR 355/r (150/100mg) twice daily (bid) for an additional 7days. Pharmacokinetics assessments were performed at days 7 and 14. For Group B, eight subjects were given BILR 355/r (150/100mg) bid for 7days. The pharmacokinetic data from Group B were also pooled with Group B subjects from other similar studies performed in parallel to this study. After co-administration with BILR 355/r, the geometric mean ratio (GMR, %) and 90% confidence interval (CI, %) of combined versus alone treatment for FTC AUC0-24,ss, Cmax,ss and C0-12,ss were 160 (154-166), 128 (121-136) and 223 (206-241), respectively; and for tenofovir AUC0-24,ss, Cmax,ss and C24,ss were 126 (121-132), 131 (117-146) and 132 (124-140), respectively. Co-administration with FTC/TDF resulted in an 18% increase in AUC0-12,ss, 14% increase in Cmax,ss and 19% increase in C12,ss for BILR 355. BILR 355 was well tolerated in this study. There was no evidence of increased risk of TFV or FTC toxicity upon co-administration of FTC/TDF with BILR 355/r. © 2010 Boehringen Ingelheim Pharmaceuticals, Inc. Basic & Clinical Pharmacology & Toxicology © 2010 Nordic Pharmacological Society.