title: Enhanced absorption and bioavailability of hydrochlorothiazide by Chinese medicines in the Zhenju antihypertensive compound.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.forename: Limin
authors.initials: L
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.forename: Yongji
authors.initials: Y
authors.lastname: Li
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Jing
authors.forename: Limei
authors.initials: L
authors.lastname: Han
authors.forename: Jianxin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001682:Biological Availability; D018938:Caco-2 Cells; D031202:Chrysanthemum; D006801:Humans; D006852:Hydrochlorothiazide / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D008516:Medicine, Chinese Traditional; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000959:Antihypertensive Agents; D010936:Plant Extracts; D006852:Hydrochlorothiazide
keywords: Zhenju antihypertensive compound; bioavailability; Caco-2 cell; hydrochlorothiazide; in situ intestinal perfusion