Absolute bioavailability of compound G004 in rats / 中国药理学通报

ABSTRACT

Aim To establish an analytical method for determination of compound G004 concentration in plasma and investigate its application to pharmacokinetics and absolute bioavailability in rats.Methods 5.0 and 2.5 mg?kg~(-1) compound G004 were given via ig and iv respectively to SD rats.Blood samples were collected at various time points after administration.Plasma concentration of compound G004 in rats was determined by LC-ESI-MS.Pharmacokinetic parameters were calculated by DAS program and absolute bioavailability was also calculated.Results The method was linear over the range of 0.02～5 mg?L~(-1)(r~2=0.9995).The recovery of compound G004 in rat plasma was more then 87%.Intra-and inter-day precision,expressed as the relative standard deviation(RSD) was less than 15%.After iv compound G004,the main pharmacokinetic parameters T_(2),CLs,V_d,AUC_((0-∞)) were(1.91?0.65) h,(0.36?0.22) L?h~(-1),(0.78?0.36) L ?kg~(-1),(9.52?3.53) mg?L~(-1)?h~(-1) respectively.The major pharmacokinetic parameters T_(max),C_(max),T_(2),AUC_((0-∞)),MRT_((0-12h)) were 0.83 h,(3.33?0.80) mg?L~(-1),(1.77?0.21) h,(10.04?2.43) mg?L~(-1)?h~(-1) and(2.75?0.31)h after ig compound G004.The absolute bioavailability was 52.69% after correction of dosage.Conclusion The method is sensitive and specific which is applicable to pharmacokinetic analysis of compound G004 in rats.