Physiologically-based pharmacokinetic (PBPK) modeling and simulation in virtual populations can uncover changes in drug disposition due to ethnic differences, providing supporting information for regulatory review and helping identify and optimize essential bridging studies.
Ethnic diversity in drug response and its impact on dosing has been well described for some drugs. A recent study of the most widely prescribed proprietary drugs in the US showed that, in around half of all cases, the recommended doses in Japan were considerably lower than both the US and European doses. Investigating the potential impact of ethnicity on pharmacokinetics often involves repeating clinical studies in different populations, which may be unnecessary in some cases.
Reducing the total number of clinical studies undertaken to secure regulatory approval without compromising patient safety is a major goal for both pharmaceutical companies and the regulatory agencies worldwide. A major global pharmaceutical company – which had identified China as a strategically important market – approached Certara® scientists to develop a virtual Chinese population so that potential differences in pharmacokinetics between populations could be simulated to assist with decision-making regarding clinical trials. This builds on the prior capabilities of the Simcyp® Simulator in capturing differences in clearance observed between Japanese and North European Caucasian subjects.3