Effect of raw Radix Rehmanniae on the pharmacokinetics of pioglitazone in rats

ABSTRACT

Raw Radix Rehmanniae [RRR] is a frequently used traditional Chinese medicine in the treatment of diabetes mellitus according to the statistics on all of the anti-diabetic formulas recorded in New National Traditional Chinese Medicine. Pioglitazone and RRR may be co-administrated for presumably enhanced therapeutic effects because of the common indications. Therefore, the aim of the study was to evaluate the effect of RRR on the pharmacokinetics of pioglitazone in healthy rats and type 2 diabetic rats. The pharmacokinetic effect of RRR on pioglitazone was studied in healthy rats and type 2 diabetic rats. A validated UPLC-MS/MS method was used to analyze the concentration of pioglitazone in blood samples. The pharmacokinetic parameters were calculated using non-compartmental analyses by Winnonlin 5.0.1. In healthy group, the pre-treatment of RRR significantly [P<0.05] reduced the C[max] but enhanced the V/F of pioglitazone; whereas in T2DM group, significant increase of C[max] and decrease of V/F and T[1/2] were found after the rats were pre-treated with RRR. However, AUC[0-t] and CL/F remained unchanged in both healthy group and T2DM group. In conclusion, co-administration with RRR could alter the pharmacokinetic profiles of pioglitazone to statistically significant levels.