Influence of Duloxetine on the in-vivo pharmacokinetics of Metoprolol in rat model

Abstract

BackgroundIt is widely accepted that Duloxetine and Metoprolol are concomitantly administered for clinical conditions like diabetic neuropathic pain and diabetic cardiovascular disorders respectively. Since these two drugs interfere with Cytochrome P2D6 (CYP2D6), there is likelihood of possible potential drug–drug interactions between these two drugs. Hence, this study was undertaken to investigate the effect of Duloxetine on the in-vivo pharmacokinetics of Metoprolol in rat models. MethodsIn-vivo pharmacokinetic studies were performed on rats. Rats were treated with Duloxetine (20 mg/kg) and Metoprolol (25 mg/kg) orally and blood samples were collected (0), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 9, 12 and 24 h post treatment. Plasma concentration of Metoprolol was estimated by Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method. ResultsDuloxetine treatment along with Metoprolol results in 3.38 fold significant (p < 0.01) increase in the area under the curve (AUC0–24) of Metoprolol, three fold significant (p < 0.01) increase in the AUC0–α of Metoprolol, 3.4 fold increase in T1/2 of Metoprolol without significant alteration in maximum concentration (Cmax) of Metoprolol. ConclusionsConcomitant administration of Duloxetine and Metoprolol orally in rat models results in increased exposure (AUC) of Metoprolol without significant increase in maximum concentration. This interaction could be of clinical significance if it is confirmed in human studies.