Pharmacokinetics of Malonato (1,2 diaminocyclohexane) platinum.
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.
D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000097:blood* / Q000652:urine
D009944:Organoplatinum Compounds; C011076:platinum(II) 1,2-diaminocyclohexane malonate