Species differences in distribution and prediction of human V(ss) from preclinical data.

摘要: Prediction of human volume distribution at steady state (V(ss)) before first administration a new drug candidate to humans has become an important part the development process. This study examines assumptions behind interspecies scaling techniques used predict V(ss) from preclinical data, namely equivalency V(ss,u) and/or f(ut) across species. In addition, several are evaluated side by using set 67 reference compounds where observed rats, dogs, monkeys, and were compiled literature plasma protein binding was determined species ultracentrifugation technique. Species similarity in or does not appear be norm among humans. Despite this, monkeys is useful can provide reasonably accurate predictions V(ss), although some approaches better than others. For example, performance common average three superior allometric techniques. considering data species, approach, any single Although mechanistic tissue composition equations available Simcyp population-based pharmacokinetic simulator did necessarily most predictions, likely need refinement, they still best opportunity for understanding prediction V(ss).