Experimental study of platinum concentration in the blood of dogs via different administration of carboplatin

Objective To investigate the pharmacokinetics in plasma of the dogs after intravenous,intra-arterial and retroperitoneal carboplatin.Methods Eighteen female dogs were randomly divided into three groups.The dogs were administrated with carboplatin at the dosage of 16.5 mg/kg intravenously,intra-arterially or retroperitoneally.The blood samples were taken at 0,5,15 minutes,and 0.5,1,2,4,8,24 and 72 hours after instillation.The competent platinum concentrations were measured with high-performance liquid chromatography(HPLC).Then the pharmacokinetic parameters were calculated and analysed.Results The peak concentration of platinum in the plasma reached instantly after instillation in the intravenous(IV) group,and at 15 minutes in the intra-arterial(IA) group and the retroperitoneal(RP) group.The maximal plasmic concentration(Cmax)of platinum was(218.20±37.20)mg/L in IV group,which was significantly higher than that in IA [(77.1±34.2)mg/L] group and RP group [(35.80±21.40)mg/L](P=0.001).The area under the plasmic concentration-time curve(AUC) was [(304.80±24.30)mg/(L·h)] in IV group,[(228.10±74.00)mg/(L·h)] in IA group and [(194.50±79.30)mg/(L·h)] in RP groups,respectively(P=0.0001).The volume of distribution(Vd)in IA and RP groups was almost the same,which was higher than that of the IV group(P=0.015).There were no significant differences for the clearance(CL) among the three groups(P=0.832).Conclusions The pharmacokinetic parameters were significantly different among three groups.The results imply that the amounts and distributions of platinum in tissues by retroperitoneal and intra-arterial carboplatin are more extensive than those by intravenous administration.