cis-Diamminedichloroplatinum (II)-procaine pharmacokinetic interaction in mice bearing P388 leukemia

M. Esposito, M. O. Vannozzi, M. Viale, C. Pellecchia, F. Merlo, A. Cadoni, S. Cafaggi, B. Parodi, R. Lerza, M. C. Poirier

Research output: Contribution to journalArticlepeer-review

Abstract

The distribution and elimination kinetics of cis-diamminedichloroplatinum (II) (DDP) in female BDF1 mice bearing 6-day P388 leukemia were investigated in the presence and absence of procaine hydrochloride (P.HCl) exposure. DDP was administered as a single i.p. dose of 8 mg/kg in a 0.9% NaCl solution 6 days after tumor inoculum. P.HCl was administered as a single i.v. dose of 40 mg/kg immediately after DDP. The combined treatment with P.HCl produced marked changes in the plasma concentration-time profile of Pt. The unbound fraction of Pt was significantly increased both in the ascites fluid and plasma following DDP+P.HCl administration. P.HCl treatment induced a significant reduction (P <0.01) in the rate constant of the protein-bound of Pt in plasma of tumored mice. Urinary excretion of Pt was unaffected by P.HCl, and there was no significant P.HCl-induced modification in the concentrations of Pt in the P388 leukemic cells. A statistically significant reduction of kidney and spleen Pt content was observed in female mice exposed to a dose of 8 mg/kg DDP+P.HCl. A similar reduction was observed in kidneys and testes of tumored mice receiving 16 mg/kg DDP along with 40 mg/kg P.HCl, which also showed lower renal and testicular cisplatin-DNA adducts after DDP+P.HCl than after DDP treatment. Potential explanations for the ability of P.HCl to interfere with the pharmacokinetics and biodistribution of DDP are discussed.

Original languageEnglish
Pages (from-to)1511-1516
Number of pages6
JournalAnticancer Research
Volume13
Issue number5 A
Publication statusPublished - 1993

Keywords

  • cis-Diamminedichloroplatinum (II)
  • Pharmacokinetics
  • Procaine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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