The authors concluded that coadministration of elbasvir and grazoprevir with SOF had no clinically meaningful effect on the pharmacokinetics of SOF and its metabolite GS-331007. Taken together with the lack of potential for SOF to perpetrate a drug-drug interaction on grazoprevir or elbasvir, these results suggest that SOF, grazoprevir, and elbasvir may be coadministered without dose adjustment.
Grazoprevir/elbasvir vs sofosbuvir
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Study Design
Sixteen (16) healthy adult male and female subjects were enrolled. In Period 1, subjects received a single oral 400-mg dose of SOF. Following an 8-day washout period, multiple oral doses of 200 mg grazoprevir and 50 mg elbasvir were coadministered daily from Days 1 to 15, inclusive, in Period 2. On Day 11, a single oral dose of SOF was coadministered with the dose of grazoprevir and elbasvir. Plasma pharmacokinetic parameters of SOF and its principal nucleoside metabolite (GS-331007) were measured in Period 1 and following the dose on Day 11 in Period 2.
Study Results
(90% CIs)] for plasma SOF AUC0-∞ and Cmax were 2.43 [2.12, 2.79] and 2.27 [1.72, 2.99], respectively. These changes in SOF exposure are not considered to be clinically meaningful based on the safety margins of SOF. The GMRs [90% CIs] for plasma GS-331007 AUC0-∞ and Cmax for the same comparison were 1.13 [1.05, 1.21] and 0.87 [0.78, 0.96], respectively. These changes in GS-331007 exposure are not considered to be clinically meaningful.
References
Marshall William L, Wendy W Yeh, Crystal Bethel-Brown, Daria Stypinski, Patrice Auger, Christine Brandquist, Dana Gill, et al. No evidence of pharmacokinetic drug-drug interaction in healthy subjects between coadministered grazoprevir (mk-5172)/elbasvir (mk-8742) and sofosbuvir [abstract no. p0910]. J Hepatol. 2015; 2: .
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