Single-dose pharmacokinetics of a novel oral platinum cytostatic drug ([OC-6-43]-bis[acetato][1-adamantylamine]amminedichloroplatinum [IV]) in pigs.

The pharmacokinetics of total platinum (Pt) were investigated after a single oral dose of (OC-6-43-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12). A dose of 3 mg/kg (n = 3) and 30 mg/kg (n = 3) was given to two parallel groups of pigs (n = three each). Pt was measured in the blood, urine and feces by atomic absorption spectrometry. Blood was sampled at specified times until 240 h, urine was obtained through a catheter at 1-h intervals until 6 h, and feces were collected until 240 h after administration. LA-12 was rapidly absorbed, as indicated by a T(max) of total Pt within 0.5-1.5 h after administration. The mean (SEM) values for maximum plasma concentration (0.060 +/- 0.025 and 0.39 +/- 0.08 mg/l) and the area under the plasma concentration vs. time curve (12.6 +/- 5.6 and 36.3 +/- 2.0 mg.h/l) increased less than proportionally to the increase in the dose. The mean (SEM) Pt urinary excretion determined over a 6-h postdose period achieved only 1.9% and 0.8% of the administered doses, respectively. Within 2 h after dosing, the renal clearance of total Pt was approximately 2-fold higher than that of creatinine (CL(cr)). Thereafter, it steadily dropped and in the last collection interval (5-6 h postdose) its value was 50% less than CL(cr). Platinum recoveries in feces over 10 days after dosing reached 0.4% and 2.6% of the administered dose, respectively. This finding indicates that the extent of absorption of both doses was high. There were no changes in results of hematology and clinical biochemistry tests. Copyright 2004 Prous Science. All rights reserved.