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- Title
THE INFLUENCE OF SERTRALINE ON THE PHARMACOKINETICS OF CARVEDILOL. A PRECLINICAL STUDY ON RATS.
- Authors
ABRUDAN, MARIA BIANCA; MUNTEAN, DANA MARIA; NEAG, MARIA ADRIANA; VLASE, LAURIAN; GHELDIU, ANA-MARIA
- Abstract
The objective of this study was to investigate the effect of multiple-dose sertraline on the pharmacokinetic profile of carvedilol in rats. Carvedilol was orally administrated in rats (3.57 mg/kg body mass (b.m.)) on the absence of sertraline or after a pre-treatment with multiple oral doses of sertraline (7.14 mg/kg b.m.). The plasma concentrations of carvedilol were estimated by HPLC-MS. After carvedilol co-administration with sertraline, an approximately 7.7-fold increase in the exposure of carvedilol was observed, considering the significantly elevated value of AUC0-∞. Moreover, an increase by 250% of peak plasma concentration was found, as well as an augmentation by 450% of the half life time of carvedilol was observed. Sertraline 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.
- Subjects
SERTRALINE; PHARMACOKINETICS; CARVEDILOL; CYTOCHROME P-450; DRUG interactions
- Publication
Farmacia, 2017, Vol 65, Issue 4, p557
- ISSN
0014-8237
- Publication type
Article