Gender-related Differences in Pharmacokinetics of Novel Prodrug of Triptolide MC002 in Rats

Objective To investigate Gender-related differences in the pharmacokinetics of MC002,a novel prodrug of triptolide.Methods MC002 was iv administrated to SD rats at 0.75 mg · kg-1.The blood samples were collected at set time before and after administration.Tissues samples were collected at 5,15,30 and 90 min after SD rats were iv given MC002 0.75 mg · kg-1.After liquid-liquid extraction,the concentrations of PG490 in biological samples were determined by HPLC-MS /MS.Pharmacokinetic parameters were calculated by DAS2.0 software.Results After iv administration of MC002 0.75 mg · kg-1 to SD rats,the AUC of active metabolite PG490 was(8046.2±634.75) and(5604.0±1140.9) μg · min · L-1,the CL was(0.089±0.01) and(0.128±0.02) L · min-1 · kg-1,respectively.Statistic difference was showed in both parameters(P0.05).The concentration of PG490 reached peak at 5 min and followed the same trend in all measured tissues in female and male rats.Conclusion There are gender difference in triptolide pharmacokinetics in rats and PG490 was eliminated more slowly in female rats than male.But no obvious difference between genders was found in concentration-time curve in tissues.