Pharmacokinetics study of oral administration CA4P in rats

OBJECTIVE To study on pharmacokinetics and metabolism of CA4 in SD rats with the oral administration CA4P.METHODS HPLC method was used for the detection of the concentration of CA4 in plasma.Column: AichromBond -1 ODS( 150 mm × 4.6 mm,5 μm);mobile phase: 0.05 mol·L -1 KH2PO4-methanol-acetonitrile( 50∶10∶40);flow rate: 1.0 mL·min -1; detection wavelength: 305 nm.After oral administration of CA4P at the dose of 20,50 and 90 mg·kg -1 in rats,the CA4 concentrations in plasma were detected.RESULTS There was good linearity in the range from 0.0155-7.7500 μg·mL -1( r = 0.9999).LOQ was 7.75 ng·mL -1; LOD was 0.3875 ng.The recovery was from 94.91%-99.85%;precision of intra-day and inter-day were 2.55%-4.87% and 5.06%-8.28%.After oral administration of CA4P in rats,the concentration-time curves of CA4 of two dosages were consistent with two-compartment model.The half lives were 48.74 min and 96.37 min; Vd were 131.39 and 450.19 L·kg -1; CL were 7.542 and 9.477 L·min -1·kg; AUC0 -t were 4.999 and 7.771 mg·L -1·min; bioavailability were 0.54% and 0.47% ,respectively.CONCLUSION The in dissolvable CA4 shows the poor absorption in body after oral administration of prodrug CA4P.It suggests that CA4 and CA4P are not applicable to oral administration directly.