Enhanced absorption and bioavailability of hydrochlorothiazide by Chinese medicines in the Zhenju antihypertensive compound

Abstract

This study was performed to investigate the influence of traditional Chinese medicines in the Zhenju antihypertensive compound (ZJAHC) on the oral absorption of hydrochlorothiazide (HCT) both in vitro and in vivo. Caco-2 cells and the in situ closed loop system were used to investigate the possible mechanism of the Chinese-Western medicine interaction on the transepithelial transport and uptake of HCT. The influence of TCMs on the pharmacokinetics and bioavailability of HCT was also studied to reveal the possible interaction in vivo. In an in situ intestinal perfusion study, the cumulative amount of HCT of ZJAHC group (506.05 μg ± 96.03) was 2.2-fold, 2.18-fold and 1.38-fold higher compared to that of the HCT group (228.29 μg ± 23.39), HCT-clonidine (CLO) group (232.13 ± 54.79 μg) and HCT-rutin (RT) group (366.08 ± 21.97 μg), respectively, after 120 min of perfusion. A pharmacokinetic analysis showed a significant increase in area under the plasma concentration-time curve (AUC) of HCT in the ZJAHC group by 2.14-fold, 2.01-fold and 1.32-fold compared to the HCT, HCT-CLO and HCT-RT groups, respectively. As a P-gp inhibitor, RT could contribute to the enhanced oral absorption of HCT in ZJAHC. The combination of traditional Chinese medicines and chemical drugs may provide a promising strategy and unique advantages to reduce the dosage and side effects of chemical drugs while maintaining an effect on hypertension.