Absolute bioavailability of compound G004 in rats

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 (r² = 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_1/2, 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_1/2, 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.