OBJECTIVE To investigate the interactive effects between Adriamycin( AMD) and chlorogenic acid ( CHA) in Beagle dog,the pharmacokinetics of AMD before and after the drug combination injection administration were studied. METHODS Beagles as the subjects were random by divided two groups,one was the combination administration group,the other was AMD only administration group. The drug serum concentration was determined by HPLC. RESULTS The linear range of AMD was between 0. 011-11. 4 μg·mL-1( r =0.9990) ; LOQ was 5. 25 ng·mL-1,there was no change from their model after drug combination administration. T1/2, Cl,AUC of these two drugs were 18. 696 and 22. 793 min,0. 029 and 0. 027 L·min-1·kg-1 ,54. 987 and 59. 53 mg·L-1·min-1 , respectively. And bioavailibility was 115. 40% . CONCLUSION There are no obvious influence of pharmacokinetics model after drug combination of AMD and CHA in Beagles,but Cl has lightly decreased,T 1/2 and AUC have increased obviously,relative bioavalibility of ADM has increased significantly( P 0. 05) . It infers that ADM therapeutic concentration has been increased by CHA after the drug combination administration.
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.
OBJECTIVE To investigate the interactive effects between Adriamycin and chlorogenic acid(CA) in rats by studying the pharmacokinetics changes before and after drug combination administration.METHODS The rats were divided into ADM,CA and drug combination groups randomly.The drug plasma concentrations in rats by HPLC-UV in different groups and different time points were determined.The pharmakinetics parameters and pharmakinetics model were calculated by DAS soft.RESULTS Both ADM and CA had good linearities between 0.011-10.500 μg·ml-1(r=0.9993) and 0.252-1260.000 μg·ml-1(r=0.9998),respectively;The LOQ were 0.011 μg·ml-1 and 0.252 μg·ml-1,respectively.There was no change of the models after drug combination administration.T1/2γ,Cl,AUC and bioavailability of these two drugs were 105.4,48.4 min;0.011,0.001 L·min-1·kg-1;167.7,6743 mg·L-1·min and 161.7%,109.5%,respectively.CONCLUSION There are no obvious changes in rats pharmacokinetics models after drug combination of AMD and CA.But T1/2,Cl and AUC have changed greatly;the bioavailability of ADM has increased significantly(P0.05);It is inferred that CA can reduce the toxicity of ADM and enhance its safety by drug combination.