Pharmacokinetic, pharmacodynamic, and drug-interaction profile of the hepatitis C virus NS5B polymerase inhibitor sofosbuvir.
^
Study Design
In a Phase 1, fixed sequence, 4-cohort study, healthy volunteers received a single dose of sofosbuvir (SOF) 400 mg before and after 14 days of Atripla (ATR, efavirenz (EFV)/ emtricitabine (FTC)/ tenofovir disoproxil fumarate (TDF) 600/200/300 mg QD; n=17, fasted), or 10 days of rilpivirine (RPV, 25 mg QD, n=17, fed), darunavir/ritonavir (DRV/r, 800/100 mg QD, n=19, fed), or raltegravir (RAL, 400 mg BID, n=19, fasted). Geometric means ratio % (GMR%, combination vs alone) of PK parameters AUCinf and Cmax for SOF and GS-331007 (circulating nucleoside metabolite of SOF), or AUCtau, Cmax, and Ctau for tenofovir (TFV), FTC, EFV, RPV, DRV/r, or RAL were evaluated against a predetermined 70-143% equivalence boundary.
Study Results
Overall, SOF was well tolerated with very few treatment-emergent events during the administration of SOF with antiretrovirals (ARVs). Co-administration of HIV ARVs and SOF did not result in clinically significant changes in SOF and/or GS- 331007 exposure. DRV/r increased SOF AUCinf by 34% and Cmax by 45% with no effect on GS-331007. SOF had no effect on the PK parameters of DRV/r.
Study Conclusions
No clinically significant drug-drug interactions were observed between sofosbuvir and antiretroviral agents
References
Kirby BJ, Symonds WT, Kearney BP, Mathias AA. Pharmacokinetic, pharmacodynamic, and drug-interaction profile of the hepatitis c virus ns5b polymerase inhibitor sofosbuvir. Clinical Pharmacokinetics . 2015; 7: 677-690.
icon on your home screen.