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• W2091796734 abstract "Aim: To study the relationship between P450 2C9 genetic polymorphisms and the pharmacokinetics of tolbutamide in Chinese subjects. Methods: P450 2C9 genotype was determined by oligonucleotide microarray. Using tolbutamide as a probe of P450 2C9 activity, P450 2C9 phenotype in 20 healthy individuals expressing the P450 2C9*1/*1, *1/*3 and *3/*3 genotypes were evaluated. After administration of 500 mg tolbutamide, plasma and urine samples were collected from each subject over a 24-h period. The tolbutamide and its metabolites’ concentrations in human plasma and urine were determined by solid-phase extraction and HPLC. Results: Tolbutamide AUC0→∞ increased by 20 and 116%, and T1/2 increased by 60 and 813%, respectively, in subjects expressing the P4502C9*1/*3 and *3/*3 genotypes compared with *1/*1 subjects. Reductions in tolbutamide oral clearance (68 and 11%) and formation clearance (39 and 3%) were detected in the *1/*3 and *3/*3 individuals, respectively, compared with */*1 subjects. Conclusion: The P450 2C9 activity was significantly reduced in *1 heterozygotes compared with *1 homozygotes, and the metabolism of tolbutamide was more severely impaired in *3/*3 individuals compared with those expressing *1/*3. Using tolbutamide as a P450 2C9 probe, P450 2C9 genotype was the major determinant of P450 2C9 phenotype." @default.
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• W2091796734 date "2005-06-01" @default.
• W2091796734 modified "2023-09-26" @default.
• W2091796734 title "Relationship of P450 2C9 genetic polymorphisms in Chinese and the pharmacokinetics of tolbutamide" @default.
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• W2091796734 doi "https://doi.org/10.1111/j.1365-2710.2005.00639.x" @default.
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