Changes in the activity of some drug metabolizing enzyme systems and cytochrome P450 quantity after multiple fluoxetine administration in rats

Authors: M. Kondeva-Burdina, M. Mitcheva, S. Deneva,

Summary. Fluoxetine is one of the most widely used selective serotonin reuptake inhibitors (SSRIs) in psychiatry. It can be used alone and in combination with other drugs. These combinations can result in adverse drug effects, connected with interactions on metabolic level. In our study, we investigated the influence of fluoxetine after multiple administration on total cytochrome P450 quantity and on drug metabolizing enzyme systems activity – ethylmorphine Ndemethylase (EMND) and aniline hydroxylase (AH). Microsomes were prepared by two different methods – ultracentrifugation and low speed centrifugation following sedimentation of the microsomal membranes in the presence of calcium ions. We found no statistically significant difference in results of total cytochrome P450 level between microsomes, prepared by both methods. As a result of the experiment, we found that after multiple administrations fluoxetine, like phenobarbital, increases significantly the level of total cytochrome P450 and the activity of EMND and AH.

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