The disposition of carboplatin in the beagle dog.
Carboplatin was administered i.v. to four groups of three male beagle dogs at doses of 3, 6, 12, and 24 mg/kg (60-580 mg/m2). Plasma samples were obtained at appropriate times and protein-free plasma ultrafiltrates (PU) were generated with Amicon Centrifree micropartition systems. Urine was collected at 24-h intervals for 96 h. PU and urine samples were analyzed for carboplatin by HPLC and for total platinum by atomic absorption spectrophotometry. Carboplatin accounted for about 90% of the free platinum in plasma. The Cmax and AUCinf values for carboplatin and for free platinum increased linearly with dose. The terminal elimination half-life and mean residence times for carboplatin and free platinum were each about 1 h. Total-body clearances for carboplatin (5.6 l/h per m2) and free platinum (5.1 l/h per m2) were constant over the dose range studied, as were the respective volumes of distribution (5.7 and 5.0 l/m2). A mean of 46% of the dose was excreted as carboplatin in 24-h urine; and by 72 h, 70% of the platinum administered was excreted in the urine. Free platinum was cleared by both renal and non-renal processes. These results show that a dose of carboplatin is rapidly excreted in the urine and that carboplatin and plasma-free platinum exhibit linear pharmacokinetics in the beagle dog.
Gaver
R C
RC
Department of Metabolism and Pharmacokinetics, Bristol-Myers Company, Syracuse, New York 13221-4755.
George
A M
AM
Duncan
G F
GF
Morris
A D
AD
Deeb
G
G
Faulkner
H C
HC
Farmen
R H
RH
D000818:Animals; D016190:Carboplatin; D002851:Chromatography, High Pressure Liquid; D004285:Dogs / Q000378:metabolism*; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D009944:Organoplatinum Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D014018:Tissue Distribution
D009944:Organoplatinum Compounds; D016190:Carboplatin