THE EFFECT OF MULTIPLE-DOSE PAROXETINE ON THE PHARMACOKINETIC PROFILE OF CARVEDILOL IN RATS
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The aim of the present study was to evaluate the effect of multiple-dose paroxetine upon the pharmacokinetic profile of carvedilol in rats. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) in the absence of paroxetine or after a pre-treatment with multiple oral doses of paroxetine (7.14 mg/kg b.m.). The plasma concentrations of carvedilol were estimated by high performance liquid chromatography-tandem mass spectrometry. After carvediol co-administration with paroxetine, an approximately 4.5-fold increase in the exposure of carvedilol was observed, considering the significantly elevated value of AUC0-∞. Furthermore, an increase by 72% of peak plasma concentration was found, as well as an augmentation by 91% of the half life time of carvedilol was observed. Paroxetine co-administration led to a significant alteration of carvedilol’s pharmacokinetic profile in rats, these effects could be explained by the existence of a drug-drug interaction mediated by CYP2D6 inhibition.
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