Evaluation of cytochrome P4502C9 metabolic activity with tolbutamide in CYP2C9*1 heterozygotes

@article{Lee2002EvaluationOC,
  title={Evaluation of cytochrome P4502C9 metabolic activity with tolbutamide in CYP2C9*1 heterozygotes},
  author={Craig R. Lee and John A. Pieper and Alan L Hinderliter and Joyce A. Blaisdell and Joyce A. Goldstein},
  journal={Clinical Pharmacology \& Therapeutics},
  year={2002},
  volume={72}
}
Multiple single‐nucleotide polymorphisms in the gene encoding cytochrome P450 (CYP) 2C9 have been identified, but the functional significance of the various putative defective genotypes in humans merits further study. 
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Aim:  To study the relationship between P450 2C9 genetic polymorphisms and the pharmacokinetics of tolbutamide in Chinese subjects.
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A novel CYP2C9 allele involving a T269C transversion in exon 2 that leads to a Leu90Pro substitution in the encoded protein was correlated with reduced plasma clearance of drugs that are substrates for CYP 2C9.
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TLDR
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THE IMPACT OF CYP 2 C 9 GENETICS AND ORAL CONTRACEPTIVES ON CYTOCHROME P 450 2 C 9 PHENOTYPE
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TLDR
It became evident that women on oral contraceptives (OCs) had slower oxidation of losartan than women without OCs, and CYP2C9 genotype and oral contraceptives both contribute to a large interindividual variation in CYP1C9 activity.
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TLDR
Data appear mature enough for the routine consideration of CYP2C9 genotypes in therapy with acenocoumarol, phenytoin, warfarin, and some other drugs, but it is advisable before the routine clinical use of these genotype data to rigorously test the benefits of genotype-based therapeutic recommendations by randomized controlled clinical trials.
Losartan and E3174 Pharmacokinetics in Cytochrome P450 2C9*1/*1, *1/*2, and *1/*3 Individuals
Study Objective. To determine if differences in the pharmacokinetics of losartan and its pharmacologically active E3174 metabolite exist among individuals expressing the cytochrome P450 (CYP)
Genetic Polymorphisms of Cytochrome P450 Enzymes and the Effect on Interindividual, Pharmacokinetic Variability in Extensive Metabolizers
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This review evaluates the potential impact of CYP genetic polymorphisms on interindividual PK variability of drugs within an EM population and concludes that optimally designed clinical trials are needed.
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The present study reports the first example of a null polymorphism in CYP2C9, which dramatically affects the half-life and clinical toxicity of phenytoin, and demonstrates the severe clinical consequences to patients with a null mutation after treatment with normal doses of phenYtoin.
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