Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele

摘要: Genetic polymorphisms in the cytochrome P450 (CYP) family are widely known to contribute interindividual differences pharmacokinetics of many drugs. Several alleles for CYP2C9 gene have been reported. Individuals homozygous Leu359 variant (CYP2C9*3) shown significantly lower drug clearances compared with Ile359 (CYP2C9*1) individuals. A male Caucasian who participated six bioavailability studies our laboratory over a period several years showed extremely low clearance two drugs: phenytoin and glipizide (both substrates CYP2C9), but not nifedipine (a CYP3A4 substrate) chlorpheniramine CYP2D6 substrate). His oral was 21% mean other 11 individuals participating study, his glipizide, second generation sulfonylurea structurally similar tolbutamide, only 188% 10 However, did differ from performed at laboratories. An additional blood sample obtained this individual determine if he possessed any or CYP2C19 allelic variants that would account poor (phenytoin glipizide) (nifedipine) (chlorpheniramine) substrates. The results genotype testing CYP2C9*3 allele possess defective alleles. This study establishes mutation is responsible glipizide/tolbutamide metabolizer phenotype.