Abstract
Pharmacokinetics (PK) and pharmacodynamics (PD) have become popular approaches for new drug evaluation. Especially, greater deal of attention has been given to the population PK/PD analysis to describe relationships for dose vs. concentration vs. response in a target patient population, and to clarify factors that can affect PK/PD of the drug (genetic, physiological, pathological, or environmental factors). Definition of PK, PD and dose-response in standard patients as well as in special populations such as geriatrics and organ dysfunction, can suggest the clinical need for individualization of dose.
In addition, simultaneous development of new drugs among the U.S., Europe and Japan becomes more and more important to save time, cost and the number of patients. Ethnic difference is one of difficult issues for international harmonization in drug development. A useful concept, “bridging study” is proposed, which is defined as a supplemental study to provide pharmacodynamic or clinical data on efficacy, safety, dosage and dose regimen in the new region that will allow extrapolation of the foreign clinical data package to the new region. The docetaxel study is a good example as a methodology to evaluate inter-ethnic differences as well as a bridging study to conduct internationally harmonized drug development. What we learned from this case is that the population PK/PD approach can play an important role as a “bridging study” for global drug development.
In conclusions, useful pharmacokinetic/pharmacodynamic information can be obtained during the premarketing clinical trials. Drug concentration monitoring in patients is essential and the population method is highly useful to analyze the sparsely sampled data. Furthermore, pharmacokinetic and pharmacodynamic approach coupled with population concepts can be an important strategy for the global drug development.
