In vitro and in vivo Drug-Drug Interaction of Losartan and Glimepiride in Rats and Its Possible Mechanism

Abstract

Background: Losartan and glimepiride are commonly used drugs to treat chronic diseases of hypertension and diabetes; they are both substrates of CYP2C9. The aim of the present study was to investigate the possible interaction of losartan and glimepiride both in vitro (rat liver microsomes) and in vivo (healthy Sprague-Dawley rats). Methods: In rat liver microsomes, 1-10 μmol/l losartan and glimepiride were coincubated, and the inhibitory effect was analyzed. In the subsequent pharmacokinetic study, 15 healthy Sprague-Dawley rats received administrations of 5 mg/kg losartan or 1 mg/kg glimepiride or a coadministration. Results: In the rat liver microsome system, glimepiride showed a slight inhibition of losartan at concentrations of 1-10 μmol/l, whereas losartan exhibited no inhibitory effect on glimepiride. In vivo, glimepiride did not modify the plasma concentration of losartan and its metabolite E-3174. The alteration of an increased AUC and C_max was observed in the pharmacokinetic parameters of glimepiride and hydroxy glimepiride. Conclusions: Glimepiride did not affect losartan pharmacokinetics in rats, while losartan potently altered glimepiride metabolism; this result was inconsistent with the in vitro outcome. The mechanism requires further investigation. In clinical settings, attention should be paid to the interaction of these two drugs in the human body as well as the possible adverse reactions of glimepiride.

Evaluation of Potential Herb-Drug Interactions Between Shengmai Injection and Losartan Potassium in Rat and In Vitro

“…Chen et al indicated that Glimepirea could increase the concentration levels of LOS and EXP3174 in the serum. The AUC 0-t of LOS was increased by 11.18%, which was lower than that of SMI ( Chen et al, 2015 ). The serum concentration of EXP3174 was associated with the degree of inhibition of CYP3A4 and CYP2C9 based on the fact that SMI could only inhibit the activity levels of the metabolic enzymes CYP3A4 and CYP2C9.…”

Pharmacokinetic Interaction Study of Ketamine and Rhynchophylline in Rat Plasma by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

“…The obvious medical interaction appeared by regulation of medical absorption, distribution, metabolism, and excretion with CYP450 as well as UDP-glucuronosyl transferase (UGT) and drug transport protein (OCT1, OCT2, OAT1, OAT3, OATP1B1, OATP1B3, P-gp, and BCRP) [ 19 ]. The binding rate of drug plasma protein was also the important factor to the interaction, especially to the approachable drug with plasma protein [ 21 ]. In addition, the constituent of Uncaria was complex; there were isorhynchophylline, corynoxeine, isocorynoxeine, corynantheine, corynoxein, isocorynoxeine, and so forth besides rhynchophylline [ 22 , 23 ].…”