Population pharmacokinetics of ravidasvir in adults with chronic hepatitis C virus infection and impact of antiretroviral treatment.
Navarat Panjasawatwong, Anchalee Avihingsanon, Caroline Menétrey, Isabela Ribeiro, Nicolas Salvadori, Alistair Swanson, Jean-Yves Gillon, Soek-Siam Tan, Sombat Thanprasertsuk, Satawat Thongsawat, Tim R Cressey, STORM-C-1 study team
Author Information
Navarat Panjasawatwong: Department of Pharmaceutical Care, Faculty of Pharmacy, Payap University, Chiang Mai, Thailand. ORCID
Anchalee Avihingsanon: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross AIDS Research Center, Bangkok, Thailand.
Caroline Menétrey: Drugs for Neglected Diseases Initiative, Geneva, Switzerland.
Isabela Ribeiro: Drugs for Neglected Diseases Initiative, Geneva, Switzerland. ORCID
Nicolas Salvadori: AMS-PHPT Collaboration, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
Alistair Swanson: Drugs for Neglected Diseases Initiative, Geneva, Switzerland.
Jean-Yves Gillon: Drugs for Neglected Diseases Initiative, Geneva, Switzerland.
Soek-Siam Tan: Department of Hepatology, Selayang Hospital, Selayang, Malaysia.
Sombat Thanprasertsuk: Department of Disease Control, Ministry of Public Health, Bangkok, Thailand.
Satawat Thongsawat: Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Tim R Cressey: AMS-PHPT Collaboration, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand. ORCID
Ravidasvir (RDV) is a novel NS5A inhibitor that exhibits potent pan-genotypic inhibition of hepatitis C virus (HCV) replication. Sofosbuvir (SOF) plus RDV was demonstrated to be efficacious and safe in adults with active HCV infection, including those living with HIV (LWHIV), in the STORM-C-1 trial. We assessed the population pharmacokinetics (PK) of RDV in a sub-study nested within STORM-C-1 conducted in Thailand and Malaysia. SOF (400 mg) plus RDV (200 mg) was administered orally once daily for 12 weeks to adults with chronic HCV infection, but without cirrhosis and for 24 weeks to those with compensated cirrhosis. Intensive and sparse PK samples were collected at 4, 8, and 12 weeks after treatment initiation. Population PK parameters of RDV and the impact of covariates were evaluated using nonlinear mixed-effects modeling. Five hundred ninety-four participants were included, 235 (40%) had compensated cirrhosis, and 189 (32%) were LWHIV. RDV plasma concentrations were best described by a two-compartment model with first-order elimination. Oral clearance (CL/F) and volume of distribution (Vd/F) parameters were allometrically scaled on fat-free mass. Concomitant antiretroviral treatment (ART) increased RDV CL/F by 30%-60%, with efavirenz-based ART having the largest impact. Females had 16% lower RDV CL/F than males, and higher albumin levels reduced RDV central volume of distribution. While several covariates impact RDV CL/F and Vd/F, the effect on RDV exposures was not clinically relevant based on the efficacy data reported in this diverse Asian adult population. There were no meaningful drug-drug interactions in adults LWHIV on ART.
