抄録
Pharmacokinetic and pharmacodynamic information of a newly developed drug is indispensable for draw up an appropriate dosing scheme. Such information obtained from healthy subjects and patients through clinical trials conducted in a current framework of Good Clinical Practice (GCP) during the pre-approval period may be applicable to the majority of patients who are to be administered the drug after approval. However, the current framework of GCP may not necessarily allows to conduct clinical trials in patients having altered pharmacokinetics and dynamics (e.g., those who possess impaired drug elimination organs, elderly and pediatric patients). They consist of the minority of patient population who required individualized drug therapy. A lack of information about fundamental pharmacokinetic parameters that are only obtainable by intravenous administration of drugs often makes it difficult to draw up an appropriate dosage scheme for patients having hepatic impairments particularly for drugs that are eliminated principally through hepatic metabolism. While abundant and ambiguous in vitro information have been generated regarding the potential impacts of pharmacogentic polymorphisms of drug metabolizing enzymes and metabolic drug interactions on the efficacy and developments of serious adverse drug reactions, few post-marketing clinical trials have been conducted for confirming in vivo consequences for the implications advocated by the in vitro studies. In this context, implementation of post-marketing clinical trials that would uncover altered pharmacokinetics and dynamics of patients due to hepatic impairments, aging, pharmacogenetic polymorphisms of drug metabolizing enzymes and metabolic drug interactions should be strongly encouraged.
