Incoming guidelines on chirality. A challenge for pharmacokinetics in drug development.
Even though scientific interest regarding enantiomeric purity of chiral drugs is continuously increasing, the availability of enantioselective assays has not developed to a level to resolve all the problems, especially those related to pharmacokinetics of chiral drugs active at low or very low plasma concentrations. Enantioselective assay in pharmacokinetics of chiral drugs is required in the case of a drug developed as a racemate in order to study the different disposition of individual stereoisomers and could be also needed in the case of the development of an individual enantiomer to ascertain whether an unidirectional enzyme mediated conversion occurs in the body. A strenuous effort is required from pharmacokinetic investigators to study enantioselective pharmacokinetics of chiral drugs, mainly for setting up adequate analytical assays. Incoming guidelines on chirality from European, USA and Japan authorities should take into account these difficulties in order to allow the investigators to select the most appropriate design, case by case.
Marzo
A
A
Drug Metabolism and Pharmacokinetic Department, Sigma-Tau S.p.A., Pomezia, Roma, Italy.
D055598:Chemical Phenomena; D002621:Chemistry; D005060:Europe; D017408:Guidelines as Topic; D007564:Japan; D010599:Pharmacokinetics; D010600:Pharmacology; D013237:Stereoisomerism; D014481:United States