Different Enzyme Kinetics of Midazolam in Recombinant CYP3A4 Microsomes from Human and Insect Sources
| Autor: | Hege Christensen, Espen Molden, Lillian W. Postvoll, Liv Mathiesen, Bjørn Winther |
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| Rok vydání: | 2009 |
| Předmět: |
Insecta
Midazolam Pharmaceutical Science Biology law.invention In vivo law Microsomes Cytochrome P-450 CYP3A Animals Humans Pharmacology (medical) Enzyme kinetics Pharmacology chemistry.chemical_classification CYP3A4 Recombinant Proteins Kinetics Enzyme chemistry Biochemistry Microsomes Liver Microsome Recombinant DNA Baculoviridae Drug metabolism |
| Zdroj: | Drug Metabolism and Pharmacokinetics. 24:261-268 |
| ISSN: | 1347-4367 |
| Popis: | In vitro drug metabolism techniques with human CYP c-DNA expressed systems are frequently used to predict human drug metabolism in vivo. The aim of this study was to compare midazolam enzyme kinetics in recombinant expressed CYP3A4 microsomes from human and insect cells. The amounts of 1'- hydroxymidazolam and 4-hydroxymidazolam formed in CYP3A4 microsomes from transfected human liver epithelial cells (T5-3A4 microsomes) and baculovirus-infected insect cells (with and without coexpressed cytochrome b(5)) were analysed by LC-MS. Enzyme kinetic parameters were estimated by nonlinear regression. Mean K(m) for the formation of 1'-hydroxymidazolam was 3- and 4-fold higher in T5-3A4 microsomes than in insect microsomes (p |
| Databáze: | OpenAIRE |
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