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

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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
Issue number5 A
Publication statusPublished - 1993


  • cis-Diamminedichloroplatinum (II)
  • Pharmacokinetics
  • Procaine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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