Pharmacokinetics of (1R,2R-diaminocyclohexane)oxalatoplatinum(II) in comparison with cisplatin following a single intravenous injection in rabbits.
The pharmacokinetics of (1R,2R-diaminocyclohexane)oxalatoplatinum(II) (1-OHP, NSC-266046), a second-generation antitumor platinum complex, was studied in rabbits and compared with that of cisplatin. The rabbits were given a single i.v. dose of 1-OHP or cisplatin (10 mumol/kg). A comparison of tissue platinum levels at 24 h postinjection showed that platinum levels were lower in the eight organs examined, which included the kidney and liver, after the injection of 1-OHP than following cisplatin administration. Plasma-decay profiles of three platinum species, that is, the unchanged species, filterable platinum, and total platinum, were examined. Plasma levels of the unchanged species and filterable platinum for 1-OHP declined more rapidly than those for cisplatin. The ratio of plasma filterable-to-total platinum indicated that the protein-binding ability of 1-OHP was greater than that of cisplatin. As for urinary excretion, amounts of the unchanged species and total platinum excreted during the 24 h period postinjection were 28% and 76% of the dose for 1-OHP and 23% and 57% of the dose for cisplatin, respectively. The renal clearance of both the unchanged species and filterable platinum in plasma for 1-OHP was about 2-fold that for cisplatin. 1-OHP is reported to be much less nephrotoxic than cisplatin. This may be due in part to its pharmacokinetic behavior or to pharmacokinetic differences resulting from chemical reactions that make 1-OHP less toxic than cisplatin.
Kizu
R
R
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Higashi
S
S
Kidani
Y
Y
Miyazaki
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077150:Oxaliplatin; D011817:Rabbits; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002945:Cisplatin