Pharmacokinetics of Malonato (1,2 diaminocyclohexane) platinum

Cancer Clin Trials. 1981 Winter;4(4):429-31.

Abstract

Malonato-(1,2 diaminocyclohexane) platinum (MP) is a new platinum analog currently undergoing phase I clinical trials. Using flameless atomic absorption spectrophotometry, the pharmacokinetics of MP were studied at five dosage levels. The drug was given as a prolonged intravenous infusion, lasting from 6 to 24 hours. Peak plasma platinum concentrations (Pt) were seen at the end of the infusion, and ranged from 1.1 microgram/ml when 3 mg/kg was given to 14-20.5 micrograms/ml at the 24-mg/kg level. Following completion of the infusion, a prolonged T1/2 beta (mean 63.5 hours) was noted. The percentage of free:total platinum was high (90-95%) at the beginning of the infusion but fell rapidly, to only 15-21% at the end of the 24-hour infusions. Urinary excretion accounted for 16-37.5% of the total administered dose. MP appears to have several pharmacokinetic features in common with cisplatin: rapid binding to protein, a prolonged terminal phase half-life involving primarily bound platinum, and incomplete excretion by the kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Half-Life
  • Humans
  • Kinetics
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / blood*
  • Organoplatinum Compounds / urine

Substances

  • Organoplatinum Compounds
  • platinum(II) 1,2-diaminocyclohexane malonate