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

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.