Boceprevir is a novel hepatitis C virus (HCV) protease inhibitor undergoing clinical investigation for use in the treatment of human HCV infection. Preclinical in vivo pharmacokinetic studies have been performed in rat, dog, and/or monkey after single administration by oral and intravenous routes for about one thousand compounds prior to the selection of boceprevir as the development candidate. In vitro pharmacokinetic assessments of metabolic stability, cell permeability, and plasma protein binding have been performed. The compound has physicochemical properties (molecular weight of 519.7 and moderate lipophilicity and H-bonding functionalities) that are borderline for good pharmacokinetic behavior. Absorption in animals ranges from 12 to 37%, indicating incomplete absorption. Based on in vitro permeability studies in Caco-2 cells, boceprevir appears to be an efflux substrate displaying a saturable efflux profile at high dosing concentrations and a reversible efflux profile in the presence of P-glycoprotein (P-gp) inhibitors. Boceprevir displayed a rather high liver/plasma average ratio of 30 in rats, indicating good uptake by the target tissue. The rat liver/plasma ratio of boceprevir appeared to be higher than those for compounds that are under clinical evaluation. Based on the preclinical pharmacokinetic data, boceprevir appears to have limited absorption, but reasonable liver distribution which is a primary factor for selecting boceprevir as a development candidate. Recent clinical proof-of-concept study confirmed that boceprevir is efficacious in reducing the viral load in patients.