In vitro and in silico Approaches to Study Cytochrome P450-Mediated Interactions

Boon Hooi Tan1, Yan Pan2, Amelia Nathania Dong3, Chin Eng Ong3

1School of Health Sciences, International Medical University, Jalan Jalil Perkasa, Bukit Jalil, Kuala Lumpur, Malaysia.
2Department of Biomedical Science, University of Nottingham Malaysia Campus, Jalan Broga, Semenyih, Selangor, Malaysia.
3School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, Selangor, Malaysia.


In vitro and in silico models of drug metabolism are utilized regularly in the drug research and development as tools for assessing pharmacokinetic variability and drug-drug interaction risk. The use of in vitro and in silico predictive approaches offers advantages including guiding rational design of clinical drug-drug interaction studies, minimization of human risk in the clinical trials, as well as cost and time savings due to lesser attrition during compound development process. This article gives a review of some of the current in vitro and in silico methods used to characterize cytochrome P450(CYP)-mediated drug metabolism for estimating pharmacokinetic variability and the magnitude of drug-drug interactions. Examples demonstrating the predictive applicability of specific in vitro and in silico approaches are described. Commonly encountered confounding factors and sources of bias and error in these approaches are presented. With the advent of technological advancement in high throughput screening and computer power, the in vitro and in silico methods are becoming more efficient and reliable and will continue to contribute to the process of drug discovery, development and ultimately safer and more effective pharmacotherapy.


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J Pharm Pharm Sci, 20 (1): 319-328, 2017

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