Mass balance study of [14C]Netanasvir Phosphate in healthy Chinese participants.

Netanasvir Phosphate is a novel second-generation NS5A inhibitor used for the treatment of chronic hepatitis C virus (HCV) infection. This study investigated the absorption, distribution, metabolism, and excretion (ADME), and the metabolite profile of [¹⁴C]Netanasvir Phosphate. In a single-dose, open-label study, six healthy Chinese male volunteers received an oral dose of 100 mg/200 µCi of [¹⁴C]Netanasvir Phosphate under fed conditions. Blood, urine, and fecal samples were collected for up to 336 h post-dose. Total radioactivity was measured using oxidative combustion and liquid scintillation counting, and the parent drug and its metabolites were analyzed by validated liquid chromatography-tandem mass spectrometry and low-energy radiometric detection and mass spectrometry methods. The pharmacokinetic profile showed a median Tmax of 5.5 h and a mean terminal half-life of 30.6 ± 8.52 h. The average total recovery of radioactivity was 97.73% ± 1.90%, with feces accounting for 97.71% of the administered dose and urine only 0.02%, indicating that fecal excretion is the primary elimination pathway. The parent drug was the predominant circulating and excreted component, representing 93.89% of plasma radioactivity and 78.78% of the administered dose in feces. Only minor metabolites were detected, including demethylated and oxidized derivatives. The drug was well tolerated, with no serious adverse events (SAEs) or dose-limiting toxicities observed. This mass balance and metabolite profiling study provides essential evidence supporting the favorable pharmacokinetic characteristics and metabolic stability of [¹⁴C]Netanasvir Phosphate and offers a scientific foundation for further clinical development in HCV-infected populations.