Simultaneous Assessment of Clearance, Metabolism, Induction, and Drug-Drug Interaction Potential Using a Long-Term In Vitro Liver Model for a Novel Hepatitis B Virus Inhibitor.

Long-term in vitro liver models are now widely explored for human hepatic metabolic clearance prediction, enzyme phenotyping, cross-species metabolism, comparison of low clearance drugs, and induction studies. Here, we present studies using a long-term liver model, which show how metabolism and active transport, drug-drug interactions, and enzyme induction in healthy and diseased states, such as hepatitis B virus (HBV) infection, may be assessed in a single test system to enable effective data integration for physiologically based pharmacokinetic (PBPK) modeling. The approach is exemplified in the case of (3S)-4-[[(4R)-4-(2-Chloro-4-fluorophenyl)-5-methoxycarbonyl-2-thiazol-2-yl-1,4-dihydropyrimidin-6-yl]methyl]morpholine-3-carboxylic acid RO6889678, a novel inhibitor of HBV with a complex absorption, distribution, metabolism, and excretion (ADME) profile.

A comparative analysis of patch-leaving decision rules in a parasitoid family.

The proximate behavioural rules adopted by parasitoid females to manage their foraging time on patches of hosts were studied, under standardized laboratory conditions, in different species (and populations) of the Trichogrammatidae (Hymenoptera) family. Seventeen species/populations were compared and the behavioural mechanisms adopted by the females were identified by means of a Cox's proportional hazards model. On average, females increased their patch-leaving tendency each time a healthy host was attacked and each time a parasitized host was rejected.