The hydroxylation of omeprazole correlates with S-mephenytoin metabolism: a population study
| Autor: | Joyce A. Goldstein, Nadia Sukhova, Linda W. Pickle, Raymond L. Woosley, James W. Harris, Jan Hewett, John D. Balian, David A. Flockhart |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Adult
Male Genotype CYP2C19 Pharmacology Hydroxylation Polymerase Chain Reaction Mixed Function Oxygenases chemistry.chemical_compound Cytochrome P-450 Enzyme System Polymorphism (computer science) Reference Values medicine Humans Pharmacology (medical) Mephenytoin Omeprazole biology Cytochrome P450 Middle Aged Cytochrome P-450 CYP2C19 Phenotype chemistry biology.protein Population study Female Aryl Hydrocarbon Hydroxylases Pharmacogenetics medicine.drug |
| Zdroj: | Clinical pharmacology and therapeutics. 57(6) |
| ISSN: | 0009-9236 |
| Popis: | We compared omeprazole and mephenytoin as probes for the CYP2C19 metabolic polymorphism. Single oral doses of omeprazole (20 mg) or mephenytoin (100 mg) were administered at least 1 week apart to 167 healthy volunteers. Mephenytoin metabolism was measured using the amount of 4′-hydroxymephenytoin and the S/R ratio of mephenytoin in an 8-hour urine collection. Omeprazole hydroxylation was measured using the ratio of omeprazole to 5′-hydroxyomeprazole in serum 2 hours after dosing. All three methods separated poor- or extensive-metabolizer phenotypes with complete concordance. Omeprazole hydroxylation correlated with the S/R ratio of mephenytoin in extensive metabolizers (r2 = 0.681; p < 0.001). Genotyping tests showed that six poor metabolizers of omeprazole were homozygous for a single base pair mutation in exon 5 of CYP2C19. These results support the hypothesis that omeprazole 5′-hydroxylation cosegregates with the CYP2C19 metabolic polymorphism. Clinical Pharmacology & Therapeutics (1995) 57, 662–669; doi |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text