Measurement of in vivo microsomal epoxide hydrolase activity in white subjects
| Autor: | Bradley M. Kerr, Lynne V. McFarland, Deanna L. Kroetz, Alan J. Wilensky, René H. Levy, Pierre Loiseau |
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| Rok vydání: | 1993 |
| Předmět: |
Adult
Male Adolescent Metabolic Clearance Rate Population Normal Distribution Epoxide Pharmacology White People chemistry.chemical_compound Pharmacokinetics Reference Values Microsomes medicine Humans Pharmacology (medical) education Epoxide hydrolase Epoxide Hydrolases education.field_of_study Carbamazepine Epoxide hydrolase activity chemistry Microsomal epoxide hydrolase Phenobarbital Female medicine.drug |
| Zdroj: | Clinical pharmacology and therapeutics. 53(3) |
| ISSN: | 0009-9236 |
| Popis: | An impairment or hereditary defect in microsomal epoxide hydrolase is considered a possible risk factor for drug and chemical toxicity. However, nothing is known about variability of in vivo epoxide hydrolase activity in humans. Our objectives were to develop and test a simple pharmacokinetic approach for measuring microsomal epoxide hydrolase activity in a population. After administration of carbamazepine-10,11 -epoxide (100 mg), oral clearance showed a nearly linear relationship to the log (transdihydrodiol/epoxide) urine ratio in the 24- to 36-hour interval (log metabolic ratio). Intrasubject variability was assessed by administering the epoxide twice to 13 subjects (1- to 4-month interval); the log metabolic ratio did not change significantly (mean difference, 11%; paired t test, p= 0.79). In 110 healthy white adults, the log metabolic ratio ranged from 1.28 to 2.05 (mean ± SD, 1.68 ± 0.155). Outliers indicating enzyme-deficient phenotypes were not observed, and the frequency distribution was unimodal normal. The log metabolic ratio detected pronounced inhibition of epoxide hydrolase by val-promide (six subjects; median ratio, 0.91) and induction by phenobarbital/phenytoin (six subjects; median ratio, 2.42). We conclude that distribution of microsomal epoxide hydrolase activity in a study group can be measured pharmacokinetically by use of carbamazepine epoxide. Clinical Pharmacology and Therapeutics (1993) 53, 306–315; doi:10.1038/clpt.1993.26 |
| Databáze: | OpenAIRE |
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