Relationship between phenytoin and tolbutamide hydroxylations in human liver microsomes
| Autor: | John O. Miners, C. J. Doecke, S. M. Pond, Maurice E. Veronese, Donald J. Birkett, L. N. Sansom, Michael E. McManus |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1991 |
| Předmět: |
Phenytoin
medicine.medical_treatment Tolbutamide Pharmacology In Vitro Techniques Hydroxylation Binding Competitive Mixed Function Oxygenases chemistry.chemical_compound Cytochrome P-450 Enzyme System Sulfaphenazole medicine otorhinolaryngologic diseases Cytochrome P-450 Enzyme Inhibitors Humans Pharmacology (medical) Mephenytoin biology Chemistry digestive oral and skin physiology Cytochrome P450 biology.organism_classification nervous system diseases stomatognathic diseases Kinetics Anticonvulsant Microsoma Immunoglobulin G Microsome biology.protein Microsomes Liver medicine.drug Research Article |
| Popis: | 1. The metabolic interaction of phenytoin and tolbutamide in human liver microsomes was investigated. 2. Phenytoin 4-hydroxylation (mean Km 29.6 microM, n = 3) was competitively inhibited by tolbutamide (mean Ki 106.2 microM, n = 3) and tolbutamide methylhydroxylation (mean Km 85.6 microM, n = 3) was competitively inhibited by phenytoin (mean Ki 22.6 microM, n = 3). 3. A significant correlation was obtained between phenytoin and tolbutamide hydroxylations in microsomes from 18 human livers (rs = 0.82, P less than 0.001). 4. Sulphaphenazole was a potent inhibitor of both phenytoin and tolbutamide hydroxylations with IC50 values of 0.4 microM and 0.6 microM, respectively. 5. Mephenytoin was a poor inhibitor of both phenytoin and tolbutamide hydroxylations with IC50 values greater than 400 microM for both reactions. 6. Anti-rabbit P450IIC3 IgG inhibited both phenytoin and tolbutamide hydroxylations in human liver microsomes by 62 and 68%, respectively. 7. These in vitro studies are consistent with phenytoin 4-hydroxylation and tolbutamide methylhydroxylation being catalysed by the same cytochrome P450 isozyme(s) in human liver microsomes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|