The authors concluded that the increases of TDF Cmax and MK-3682 and M6 exposures were modest and not considered to be clinically meaningful. They state that the co-administration of MK-3682 and TDF is supported by their findings.
Uprifosbuvir vs dolutegravir, raltegravir, rilpivirine, or tenofovir disoproxil fumarate
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Study Design
This was a four-part open label drug interaction study in which 54 healthy subjects were enrolled. Parts 1-3 assessed the one way interaction of multiple doses of MK-3682 on single doses of dolutegravir (DTG), raltegravir (RTG) and rilpivirine (RPV), respectively. In period 1, single doses of ARV were administered. Following a washout period of three days (for dolutegravir and raltegravir) or ten days (for rilpivirine). In period 2, subjects received 300 mg of MK-3682 once daily for seven days to achieve steady state and single doses of ARV on day seven. Part four assessed the two-way interaction of multiple doses of MK-3682 and tenofovir (TDF). In period 1, subjects received 300 mg of TDF once daily for seven days, followed by a washout period of 7 days, and received MK-3682 300 mg once daily for seven days in period two. In period three, subjects received MK-3682 300 mg once daily and TDF 300 mg once daily for seven days. Blood samples were collected for PK assessment of ARV in parts 1-4 and MK-3682 and its circulating metabolite M6 in part 4.
Study Results
Multiple doses of MK-3682 increased TDF Cmax by 41% with no meaningful effect on AUC or C24. Coadministration of TDF increased MK-3682 AUC and Cmax by 24% and 55% respectively and M6 Cmax by 21% with minimal effect on M6 AUC.
References
W Gao, S Glasgow, J Luk, E Rhee, W Marshall, N Kim, et al. No clinically relevant interaction of mk-3682 with the hiv medications: dolutegravir, raltegravir, rilpivirine and tenofovir disoproxil fumarate. 17th International Workshop On Clinical Pharmacology Of Hiv And Hepatitis Therapy. Washington, DC, USA. ; 2016.
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