Pretreatment of Shaoyao Gancao Decoction () alters pharmacokinetics of intravenous paclitaxel in rats.

Objective: To investigate the effect of Shaoyao Gancao Decoction (SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats. Methods: Paclitaxel was intravenously administered to rats (3 mg/kg) with or without the concomitant administration of SGD (752 mg/kg, a single day or 14 consecutive days pretreatment). The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography (UPLC) method for the pharmacokinetic study. The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0. Results: The pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD. The area under the curve (AUC(0-t), from 4 820 +/- 197 to 4 205 +/- 186 ng.mL(-1).(-1)) and AUC(0-a) (from 5 237 +/- 280 to 4 514 +/- 210 ng.mL(-1).(-1)) significantly decreased in response to the 14-day pretreatment with SGD. The values of V-dss (L/kg) were 10.74 +/- 1.08 and 9.35 +/- 0.49, those of CL (L/kg) were 0.67 +/- 0.03 and 0.57 +/- 0.03 and the t(1/2) (h) values were 11.17 +/- 0.84 and 11.32 +/- 0.93, respectively, for the 14-day SGD pretreatment and intravenous paclitaxel alone. The AUC(0-t) and AUC(0-a) values decreased by 13% and 14% (P < 0.01), respectively. The area under the curve decreased signifificantly (P < 0.01), and the total clearance increased by 1.2-fold (P < 0.01), after 14 consecutive days of pretreatment with SGD. A single-day pretreatment with SGD did not signifificantly affect the pharmacokinetic parameters of paclitaxel. Conclusions: SGD administration for 14 consecutive days increased the metabolism of paclitaxel, while a 1-day pretreatment had little effect. The results would contribute important information to the study on interaction between Chinese medicines and chemotherapy and also help to utilize SGD better in the adjunctive therapy of cancer patients.