The influence of gender on metabolic activity of enzymatic system of cytochrome P450 in the model of isolated perfused rat liver.
| Authors | |
|---|---|
| Year of publication | 2006 |
| Type | Article in Periodical |
| Magazine / Source | Homeostasis in Health and Diseases |
| MU Faculty or unit | |
| Citation | |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | cytochrome P450; the isolated perfused liver; influence of gender |
| Description | Interindividual variability of activity of oxidative and conjugating enzymes, especially the system of cytochrome P450, can be based on many different factors i.e. gender, age, genetic factors or interactions between simultaneously applied drugs. Such a variability may result in a different pharmacoterapeutical effectivity, adverse effects or toxicity of apllied drug. A suitable model for investigations on the activity of hepatic CYPs 450 and biotransformation processes is represented by the isolated perfused liver. As we expected, the activity of CYP subfamilies differed due to gender. CYP 2D2 activity in rat females was significantly higher than in males (Fig. 1). Also the final concentration of a marker metabolite (dextrorphan) in females was higher only in CYP 2D2. The elevation was 5,7% in the 30th min, 33% in the 60th min and 34% in the 120th min. In contrast activity in CYP 3A subfamily in females was lower than in males. Next two isoforms of CYP450, used as markers were tolbutamid (CYP2C6 – metabolite 4-hydroxytolbutamid) and phenacetin (CYP1A2 – metabolite paracetamol). They showed dramatically lower activity when compared to CYP 2D2, and female metabolization was slower than in males. Thus, the obtained results suggest that the activity of CYP 450 is gender dependent and different dosing schemes for males and females should be used when administering drugs metabolized by CYP 450. |
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