Effects of berberine on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism.
BACKGROUND
Losartan and berberine (BBR) are often simultaneously used for the treatment of senile diabetic nephropathy in clinics. However, the potential herb-drug interaction between losartan and BBR is unknown.


OBJECTIVE
This study investigates the influence of BBR on the pharmacokinetics of losartan and EXP3174, and investigates the effects of BBR on the metabolic stability of losartan.


METHODS
The pharmacokinetic profiles losartan and EXP3174 of orally administered losartan (10 mg/kg) with and without pretreatment with BBR (20 mg/kg) within 24 h were determined in Sprague-Dawley rats. The inhibitory effects of BBR on the metabolic stability of losartan were investigated using rat liver microsomes.


RESULTS
The Cmax(1.26 ± 0.37 versus 1.96 ± 0.45 mg/L) and the AUC(0-t)(8.25 ± 0.89 versus 12.70 ± 1.42 mg h/L) of losartan were significantly (p < 0.05) increased by BBR compared to the control, while the Cmax(0.97 ± 0.15 versus 0.77 ± 0.06 mg/L) of EXP3174 was significantly decreased compared to the control (p < 0.05). The Tmaxof losartan was prolonged from 0.41 ± 0.12 to 0.52 ± 0.18 h, but the difference was not significant. However, the Tmaxof EXP3174 was decreased significantly (p < 0.05) from 8.14 ± 0.36 to 3.33 ± 0.28 h. The metabolic stability of losartan was increased from 37.4 to 59.6 min.


CONCLUSIONS
We infer that BBR might increase the plasma concentration of losartan and decrease the concentration of EXP3174 through inhibiting the activity of CYP3A4 or CYP2C9.
a Department of Endocrinology , Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai , P.R. China.
Hong
H
Li
a Department of Endocrinology , Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai , P.R. China.
Lu
L
Liu
b Biliary Tract Surgery Department 1, Eastern Hepatobiliary Surgery Hospital , Second Military Medical University , Shanghai , P.R. China.|c Ningbo Cancer Hospital, Shanghai Wu Meng Chao Cancer Center , Ningbo City , Zhejiang Province , P.R. China.
Lei
L
Xie
d Department of Paediatrics , Ningbo Women and Children's Hospital , Ningbo , Zhejiang Province , P.R. China.
Dongmei
D
Gan
b Biliary Tract Surgery Department 1, Eastern Hepatobiliary Surgery Hospital , Second Military Medical University , Shanghai , P.R. China.
Xiaoqing
X
Jiang
D000818:Animals; D001599:Berberine / Q000097:blood* / Q000493:pharmacokinetics; D041743:Herb-Drug Interactions / Q000502:physiology*; D019808:Losartan / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001599:Berberine; C066026:losartan carboxylic acid; D019808:Losartan
CYP450; LC–MS; drug–drug interaction