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

• Published in: Basic & clinical pharmacology & toxicology 2011-03, Vol.108 (3), p.163-170
• Main Authors: Huang, Fenglei, Scholl, Paul, Huang, David B., MacGregor, Thomas R., Taub, Mitchell E., Vinisko, Richard, Castles, Mark A., Robinson, Patrick
• Format: Article
• Language: English
• Subjects: Adenine - administration & dosage; Adenine - adverse effects; Adenine - analogs & derivatives; Adenine - blood; Adenine - pharmacokinetics; Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - adverse effects; Anti-HIV Agents - blood; Anti-HIV Agents - pharmacokinetics; Antiretroviral Therapy, Highly Active - adverse effects; Azepines - adverse effects; Azepines - blood; Azepines - pharmacokinetics; BID protein; Biological and medical sciences; Cross-Over Studies; Data processing; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - blood; Deoxycytidine - pharmacokinetics; Drug Interactions; Emtricitabine; Female; Half-Life; HIV Protease Inhibitors - administration & dosage; HIV Protease Inhibitors - adverse effects; HIV Protease Inhibitors - blood; HIV Protease Inhibitors - pharmacokinetics; Humans; Male; Medical sciences; Metabolic Clearance Rate; Middle Aged; Organophosphonates - administration & dosage; Organophosphonates - adverse effects; Organophosphonates - blood; Organophosphonates - pharmacokinetics; Pharmacokinetics; Pharmacology. Drug treatments; Pyridines - adverse effects; Pyridines - blood; Pyridines - pharmacokinetics; Reproducibility of Results; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - adverse effects; Reverse Transcriptase Inhibitors - blood; Reverse Transcriptase Inhibitors - pharmacokinetics; Ritonavir - administration & dosage; Ritonavir - adverse effects; Ritonavir - blood; Ritonavir - pharmacokinetics; Tenofovir; Toxicity; Young Adult
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2010.00636.x

:  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 (200/300 mg) once daily (QD) for 7 days and then co‐administered with BILR 355/r (150/100 mg) twice daily (bid) for an additional 7 days. Pharmacokinetics assessments were performed at days 7 and 14. For Group B, eight subjects were given BILR 355/r (150/100 mg) bid for 7 days. 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.