Effects of type 2 diabetes mellitus on the pharmacokinetics of berberine in rats

• Published in: Pharmaceutical biology Vol. 55; no. 1; pp. 510 - 515
• Main Authors: Jia, Yuzhen, Xu, Binger, Xu, Jisen
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2017; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Administration, Oral; Animals; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - blood; Antihypertensive Agents - pharmacokinetics; Area Under Curve; Berberine; Berberine - administration & dosage; Berberine - blood; Berberine - pharmacokinetics; Biomarkers - blood; Blood Glucose - drug effects; Blood Glucose - metabolism; Chromatography, Liquid; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - drug therapy; Diet, High-Fat; Dosage; Glucose; Half-Life; High fat diet; Hyperlipidemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - blood; Hypoglycemic Agents - pharmacokinetics; Hypolipidemic Agents - administration & dosage; Hypolipidemic Agents - blood; Hypolipidemic Agents - pharmacokinetics; LC-MS/MS; Male; Metabolic Clearance Rate; Peripheral blood; Pharmacokinetics; Rats, Sprague-Dawley; Reproducibility of Results; Streptozocin; T2DM; Tandem Mass Spectrometry; Berberine; LC-MS/MS; T2DM; Pharmacokinetics
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2016.1255649

Context: Berberine is an active alkaloid isolated from Rhizoma coptidis [Coptis chinensis Franch. (Ranunculaceae)] that is widely used for the treatment of diabetes, hyperlipidemia and hypertension. However, the pharmacokinetics of berberine in normal rats and type 2 diabetes mellitus (T2DM) model rats are not clear. Objective: This study compares the pharmacokinetics of berberine between normal and T2DM model rats. Materials and methods: The T2DM model rats were fed with high fat diet for 4 weeks, induced by low-dose (30 mg/kg) streptozotocin for 72 h and validated by determining the peripheral blood glucose level. Rats were orally treated with berberine at a dose of 20 mg/kg and then berberine concentration in rat plasma was determined by employing a sensitive and rapid LC-MS/MS method. Results: The significantly different pharmacokinetic behaviour of berberine was observed between normal and T2DM model rats. When compared with the normal group, C max , t 1/2 and AUC (0- t ) of berberine were significantly increased in the model group (17.35 ± 3.24 vs 34.41 ± 4.25 μg/L; 3.95 ± 1.27 vs 9.29 ± 2.75 h; 151.21 ± 23.96 vs 283.81 ± 53.92 μg/h/L, respectively). In addition, oral clearance of berberine was significantly decreased in the model group (134.73 ± 32.15 vs 62.55 ± 16.34 L/h/kg). Discussion and conclusion: In T2DM model rats, the pharmacokinetic behaviour of berberine was significantly altered, which indicated that berberine dosage should be modified in T2DM patients.