Drug Metabolosm, Bristol-Myers Squibb, Princeton, NJ 08543, USA. david.rodrigues@bms.com
Drug metabolism and disposition: the biological fate of chemicals 2005 NovThe market withdrawals of rofecoxib (Vioxx) and valdecoxib (Bextra) have focused considerable attention on the side effect profiles of cyclooxygenase (COX) inhibitors. As a result, attempts will be made to identify risk factors in the hope that physicians might be able to ensure patient safety. At first glance, CYP2C9 genotype might be considered a risk factor because many COX inhibitors are CYP2C9 substrates in vitro. This observation has led some to hypothesize that a reduction in clearance, in subjects expressing variant forms of the enzyme (e.g., CYP2C9*1/*3 or CYP2C9*3/*3 genotype), will lead to increased exposure and a greater risk of cardiovascular or gastrointestinal side effects. For any drug, however, one has to consider all clearance pathways. Therefore, a number of COX inhibitors were surveyed and it was determined that CYP2C9 plays a relatively minor role in the overall clearance (
A David Rodrigues. Impact of CYP2C9 genotype on pharmacokinetics: are all cyclooxygenase inhibitors the same? Drug metabolism and disposition: the biological fate of chemicals. 2005 Nov;33(11):1567-75
PMID: 16118328
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