In addition to efficacy, factors critical for development of a successful drug candidate include good drug metabolism and pharmacokinetic (DMPK) properties along with minimal toxicity. Generally, inferior DMPK properties result in poor absorption, high clearance and have been attributed to the failure of oral drugs during the clinical development. In addition, potential of drug interactions or their inadequate understanding can complicate successful drug development. The prediction of human pharmacokinetics and metabolism of drugs is critical to advance the right compounds into clinical settings. Though, use of in vitro data to extrapolate in vivo has aided the effort allowing for prediction of pharmacokinetic parameters, with our current understanding, the translation to a clinical outcome is far from accurate.
I plan to build a research program that is aimed at improving our understanding and prediction of DMPK properties of drugs using in silico and in vitro tools. Specifically my research will be focused on understanding mechanisms of CYP mediated drug-drug interactions (DDIs); pharmacokinetic modeling of CYP-dependent DDIs; in vitro-in vivo correlations of drug clearance and drug interaction and the effect of CYP polymorphisms on drug clearance.