Pharmacokinetics of (1R,2R-diaminocyclohexane)oxalatoplatinum(II) in comparison with cisplatin following a single intravenous injection in rabbits.
Cancer Chemother Pharmacol
; 31(6): 475-80, 1993.
Article
em En
| MEDLINE
| ID: mdl-8453687
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organoplatínicos
/
Cisplatino
/
Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
1993
Tipo de documento:
Article
País de afiliação:
Japão