[Verification of Pharmacokinetic Approaches in Prior Drug Development].

[Verification of Pharmacokinetic Approaches in Prior Drug Development]. Yakugaku Zasshi. 2019;139(3):437-460 Authors: Iga K Abstract In this review, 9 compounds with insufficient absorption characteristics, safety or efficacy were selected from among the compounds for which the author was in charge of development between 2000 and 2005, in order to evaluate the pharmacokinetic (PK) approaches used to develop these compounds. Optimization of the PK characteristics of a compound at the early stage of chemical design was found to be the most important factor for successful development. For example, (i) selecting class I or II drugs in the biopharmaceutical classification system, while avoiding efflux transporters, and introducing an appropriate dissociation moiety into a compound to make it soluble lead to sufficient drug absorption; (ii) designing compounds whose production of reactive metabolites, such as acyl glucuronide, does not largely affect total metabolism, yet helps to prevent abnormal PK caused by reactive metabolites. Other factors include (i) selection of a drug efficacy evaluation system based on the correct understanding of the relationship between PK and pharmacodynamics (PD) helps to solve species differences in PD; (ii) the establishment of a nonclinical study based on the identification of the involvement of specific cytochrome P450 molecules in the total metabolic clearance of a drug (fm,CYPs) helps to solve species d...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research