PLATINUM CONCENTRATIONS IN UTERUS AND SERUM AFTER INTERNAL ILIAC ARTERIAL INFUSION OF PLATINUM COMPOUNDS IN RABBITS

Objective: To compare three platinum compounds, and study the pharmacokinetics of these compounds after systemic and intra-arterial infusion. Methods: Adult female rabbits received infusions of 1.7 mg/kg cisplatin, 10 mg/kg carboplatin, or 6 mg/kg cis-diammine(glycolato)platinum (254-S) via the internal iliac artery or jugular vein. The doses were equitoxic. Platinum tissue concentration in uterus and platinum serum levels were measured after internal iliac arterial or intravenous (TV) infusion with these platinum compounds. Results: Platinum uterine concentration after intra-arterial infusion was significantly higher than that after IV infusion for each drug (P < .05). The ratios of platinum uterine concentration after intra-arterial infusion to those after IV infusion were 2.24 for cisplatin, 1.83 fbr carboplatin, and 1.67 for 254-S measured 20 minutes after drug administration. The area under the curve of filtrated platinum (mu g/mL hours) was significantly lower for cisplatin compared with carboplatin and 254-S in both infusion methods (1.5 for cisplatin, 32.1 for carboplatin, and 16.0 for 254-S after IV administration, and 0.8, 30.9, and 15.2 after intra-arterial administration, respectively). Conclusion: Cisplatin produced the highest ratio of uterine to serum concentration of platinum after intra-arterial infusion.