Stereoselective disposition of mianserin is related to debrisoquin hydroxylation polymorphism
| Autor: | Marja-Liisa Dahl, Carl-Eric Elwin, Marianne Gyllenpalm, Karin Andréasson, Leif Bertilsson, Christina Alm, Gunnel Tybring |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
Male CYP2D6 Metabolite Debrisoquin Administration Oral Mianserin Pharmacology Hydroxylation White People Mixed Function Oxygenases chemistry.chemical_compound Cytochrome P-450 Enzyme System Pharmacokinetics Oral administration medicine Humans Pharmacology (medical) Chromatography High Pressure Liquid Sweden Polymorphism Genetic Stereoisomerism Middle Aged Cytochrome P-450 CYP2D6 chemistry Debrisoquine Female Mephenytoin medicine.drug |
| Zdroj: | Clinical Pharmacology and Therapeutics. 56:176-183 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1038/clpt.1994.121 |
| Popis: | The pharmacokinetics of mianserin and its main metabolite desmethylmianserin were studied in poor and extensive metabolizers of debrisoquin and of S-mephenytoin after a single oral dose of racemic mianserin. The debrisoquin metabolic ratio (MR) correlated significantly with area under the serum concentration-time curves (AUC) for (+/-)-mianserin and (+/-)-desmethylmianserin. Enantioselective high-performance liquid chromatographic analysis of mianserin showed that debrisoquin MR was related to AUC(0-12) for S(+)-mianserin (rs = 0.87; p = 0.001; n = 15) but not for R(-)-mianserin. The ratio between the AUC(0-12) for S(+)-mianserin and that for R(-)-mianserin was higher in poor metabolizers than in extensive metabolizers. Two extremely rapid extensive metabolizer subjects had the lowest mianserin S/R ratios. No differences in the pharmacokinetics of mianserin or desmethylmianserin were found between extensive metabolizers and poor metabolizers of S-mephenytoin. The study shows that the elimination of both mianserin and its main metabolite desmethylmianserin is dependent on CYP2D6 activity. Furthermore, the CYP2D6-dependent elimination of mianserin shows marked enantioselectivity for the more active S(+)-enantiomer of mianserin. |
| Databáze: | OpenAIRE |
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