Pharmacokinetics of Purine Benzamides PLB-E and PLB-P in Rats

OBJECTIVE To establish a method for the determination of the concentrations of anti-tumor lead compounds purine benzamides PLB-E and PLB-P in rat plasma by HPLC and apply to study pharmacokinetics.

METHODS The established HPLC was used to determine the plasma drug concentrations of rats at different time points after intravenous administration of 5, 10, 20 mg·kg^–1 (low, medium, high doses) of PLB-E and PLB-P, and the pharmacokinetic parameters of each compound were calculated using DAS 3.3.0 software.

RESULTS PLB-E and PLB-P had good linear relationship in the range of 2–120, 3–60 μg·mL^–1, respectively(r²>0.999). The RSD of inter-day and intra-day precision were <15%. The extraction recoveries were 87.48%–92.84% and 88.24%–92.60%, respectively. The main pharmacokinetic parameters of PLB-E and PLB-P after a single intravenous injection of 5, 10, 20 mg·kg^–1 were as follows, the average C_max was (20.30±2.39), (40.63±3.40), (63.62±7.55)mg·L^–1 and (13.21±1.40), (24.87±1.33), (32.83±0.65)mg·L^–1, respectively. AUC_(0-∞) were (104.67±48.39), (177.42±84.11), (194.32±91.48)mg·h·L^–1 and (106.75±54.21), (179.90±93.59), (253.56±126.17)mg·h·L^–1, respectively. T_max of each dose was 0.08 h.

CONCLUSION The HPLC method established in this study meets the requirements for the determination of biological samples through methodological verification, which is applicable to the determination of the concentration of PLB-E and PLB-P in rat plasma and the pharmacokinetic study. The pharmacokinetic process of PLB-E and PLB-P in rats conforms to the two-compartment model, and conforms to the nonlinear kinetic elimination.