Potency and plasma protein binding of drugs in vitro-a potentially misleading pair for predicting in vivo efficacious concentrations in humans.

ABSTRACT: In drug discovery or preclinical stages of development, potency parameters such as IC₅₀, K _i, or K _d in vitro have been routinely used to predict the parameters of efficacious exposure (AUC, C _min, etc.) in humans. However, to our knowledge, the fundamental assumption that the potency in vitro is correlated with the efficacious concentration in vivo in humans has not been investigated extensively. Thus, the present review examined this assumption by comparing a wide range of published pharmacokinetic (PK) and potency data. If the drug potency in vitro and its in vivo effectiveness in humans are well correlated, the steady-state average unbound concentrations in humans [C _{u_ss.avg}

SUBMITTER: Yim DS 

PROVIDER: S-EPMC6609267 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature