Publication details
POHLAVNÉ ROZDIELY METABOLICKEJ AKTIVITY CYP2D2 PO PREMEDIKÁCII BUPROPIONOM NA MODELE IZOLOVANEJ PERFUNDOVANEJ PEČENE
| Title in English | Gender-dependent influence of bupropion on the activity of hepatic cytochrome |
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| Authors | |
| Year of publication | 2007 |
| Type | Article in Periodical |
| Magazine / Source | Psychiatrie |
| MU Faculty or unit | |
| Citation | |
| Field | Pharmacology and pharmaceutical chemistry |
| Keywords | Cytochrome P450; bupropion; isolated perfused liver |
| Description | Adjustment of the dosage of a drug for an individual patient, individualisation and optimisation of therapy to prevent adverse effects, and to decrease duration as well as costs of treatment belong to the basic principles of the modern pharmacotherapy. Numerous factors are known to influence the pharmacokinetics of drugs and especially the drug metabolism in the liver. Interindividual variability in the activity of oxidative and conjugative enzymes, especially of the cytochrome P450 system, can be based on various endogenous as well as exogenous influences like gender, age, genetic factors, pathological state or interactions between the concurrently applied drugs. Such variability may result in a different pharmacological effect, adverse reactions or toxicity of administered drugs. Only scarce data are available about the gender-dependency of metabolism of individual drugs including psychotropics. Bupropion is an antidepressant of the aminoketone class, chemically unrelated to tricyclics or selective serotonin reuptake inhibitors (SSRIs). It is similar in structure to the stimulant cathinone, anorectic diethylpropion and to phenethylamines in general. Bupropion is both a dopamine and a norepinephrine reuptake inhibitor. The antidepressant effect of bupropion is considered to be mediated primarily by its dopaminergic and noradrenergic action. Bupropion has also been shown to act as a competitive alfa3beta4 nicotinic antagonist; the alfa3beta4-antagonism has been shown to weaning addictions in studies of other drugs such as ibogaine. This alfa3beta4-antagonism of bupropion correlates quite well with the observed effect of weaning addicts. Bupropion is metabolized in the liver. There are known at least three active metabolites: hydroxybupropion, threohydrobupropion and erythrohydrobupropion. Quite a large number of drugs show clinically significant interactions with bupropion. This may be due to interactions with drugs that are metabolized by CYP2D6 because bupropion was recently shown to inhibit CYP2D6 activity. Although bupropion is not metabolized by CYP2D6, there is a certain potential for interaction when bupropion is co-administered with other drugs metabolized by this isoenzyme. The isolated perfused liver can be used as a suitable model for studies on the activity of hepatic CYPs and biotransformation processes (1, 2). The histological microstructure, as well as the system of biochemical and physiological links is preserved. The main advantage of this method, in comparison with other methods used for measuring the CYP activity (microsomal liver fractions, hepatocytes culture, recombinant human CYPs), are conditions resembling physiological situation in the organism. |
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