Biomaterial Database

Effects of berberine on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism. 2016

Hong Li, and Lu Liu, and Lei Xie, and Dongmei Gan, and Xiaoqing Jiang

a Department of Endocrinology , Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai , P.R. China.

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 Tmax of losartan was prolonged from 0.41 ± 0.12 to 0.52 ± 0.18 h, but the difference was not significant. However, the Tmax of 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.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001599	Berberine	An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal.	Umbellatine
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D019808	Losartan	An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.	2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol,Cozaar,DuP-753,Losartan Monopotassium Salt,Losartan Potassium,MK-954,MK954,DuP 753,DuP753,MK 954,Monopotassium Salt, Losartan,Potassium, Losartan,Salt, Losartan Monopotassium
D041743	Herb-Drug Interactions	The adverse or beneficial effect of MEDICINAL HERBS on the activity, metabolism, or toxicity of PHARMACEUTICALS.	Adverse Herb-Drug Interactions,Beneficial Herb-Drug Interactions,Drug-Herb Interactions,Drug-Plant Interactions,Herbal Drug Interactions,Plant-Drug Interactions,Adverse Herb Drug Interactions,Adverse Herb-Drug Interaction,Beneficial Herb Drug Interactions,Beneficial Herb-Drug Interaction,Drug Herb Interactions,Drug Interaction, Herbal,Drug Interactions, Herbal,Drug Plant Interactions,Drug-Herb Interaction,Drug-Plant Interaction,Herb Drug Interactions,Herb-Drug Interaction,Herb-Drug Interaction, Adverse,Herb-Drug Interaction, Beneficial,Herb-Drug Interactions, Adverse,Herb-Drug Interactions, Beneficial,Herbal Drug Interaction,Interaction, Adverse Herb-Drug,Interaction, Beneficial Herb-Drug,Interaction, Drug-Herb,Interaction, Drug-Plant,Interaction, Herb-Drug,Interaction, Herbal Drug,Interaction, Plant-Drug,Interactions, Adverse Herb-Drug,Interactions, Beneficial Herb-Drug,Interactions, Drug-Herb,Interactions, Drug-Plant,Interactions, Herb-Drug,Interactions, Herbal Drug,Interactions, Plant-Drug,Plant Drug Interactions,Plant-Drug Interaction