Pharmacokinetics behavior of raltitrexed in rats after repeatedly injected with Huangqi injection / 中国中药杂志

ABSTRACT

In this study, the variation of pharmacokinetics behavior of raltitrexed (RTX) in rats after repeatedly injected with Huangqi injection was investigated. Twelve SD rats were divided into two groups the multidose group and the RTX group. Rats in multidose group were iv. injected with Huangqi injection (dose of 1.575 mL x kg(-1)) everyday at 8 am for a week, and had free accesses for food and water. The rats were fasted for food but not water since 8 h before the eighth day. At the eighth morning, firstly, rats were injected with Huangqi injection (dose of 1.575 mL x kg(-1)), and 5 min later, were injected with RTX (dose of 0.467 mg x kg(-1)); rats in RTX group were not disposed in the previous seven days, also had free accesses for food and water, and were iv. injected with raltitrexed at the same time as Multidose group at the eighth day morning. Rat plasma was collected at different time and processed with methanol to precipitate the protein before HPLC assays. The pharmacokinetics parameters for two groups were calculated by software 3P97. Through the observation of drug concentration in plasma and time curve, we found that at almost every time point the concentration of RTX in plasma in multidose group was lower than the RTX group. When comparing the pharmacokinetics parameters between the multidose group and the RTX group, the average of AUC(0-t) and half-life(t1/2) of multidose group were decreased from 56 080 microg x min x L(-1) and 15.07 min to 35 834 microg x min x L(-1) and 8.95 min, respectively, while the clearance (CL) was increased from 0.51 to 0.83 mL x h(-1). Therefore, it could be deduced that repeatedly injected with AR injection may influence the renal excretion and glycometabolism of RTX, thus change pharmacokinetics behavior of raltitrexed in rats plasma. This result may give us a hint to prudantly manage the drug combination of RTX and Huangqi injection.