Herb-Drug Interaction of Quercetin on the Pharmacokinetics of Losartan in Rats: A High-Performance Thin-Layer Chromatography Study

Abstract

Losartan potassium (LOS), used in the treatment of hypertension, is metabolized primarily by cytochrome P450. This study investigates the effect of quercetin (QU), a CYP3A4 inducer, on the pharmacokinetics of LOS in rats. A rapid, sensitive high-performance thin-layer chromatography (HPTLC) method was developed and validated for the bioanalysis of losartan using olmesartan as internal standard (IS). The salting-out assisted liquid—liquid extraction (SALLE) employing acetonitrile and MgCl2 gave high recovery of LOS (>90%). HPTLC separation, achieved on silica gel 60 F254 plates employing toluene—ethyl acetate—acetone—formic acid (4:4:1:0.5 V/V) as the mobile phase, with densitometric analysis at 240 nm, gave good linearity (50–1200 ng mL-1) with high intra-day and i nter-day precision. LOS in plasma samples was stable when stored under different stability conditions. The pharmacokinetics of LOS was found to be significantly altered when co-administered with QU: C max = 809.8 ± 4.1 at 40 min (t max) to C max = 1124.8 ± 86.6 ng mL-1 at 120 min (t max). This study indicates the chances of herb—drug interaction when LOS is co-administered with QU, leading to its increased bioavailability, potentiating its side effect/toxic manifestation. As QU is abundantly present in herbs and dietary food, patients of LOS therapy need to be cautious while concurrently consuming herbal preparations containing QU. This study also demonstrates the utility of HPTLC as an effective tool for pharmacokinetics study for the estimation of herb—drug interactions.