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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1984-10-17
pubmed:abstractText
Preclinical studies were performed in mice, rats and dogs of cis-diamminedichloroplatinum(II) (CDDP) and its derivatives cis-1,1-di(aminomethyl) cyclohexane platinum(II) sulphate (TNO-6), cis-diammine-1,1-cyclobutanedicarboxylate platinum(II) (CBDCA) and cis-dichloro, trans-dihydroxybis-isopropylamine platinum(IV) (CHIP). In mice toxicity and antitumour activity were determined. All three derivatives were at least as toxic as CDDP for haemopoietic stem cells and were less active than CDDP against the mouse tumours leukaemia L1210 and osteosarcoma C22LR. Toxicology studies in rats revealed no renal toxicity after a single dose of TNO-6. Fractionated doses of TNO-6 and CBDCA did cause renal toxicity but less than CDDP. CHIP produced little or no kidney damage. In dogs, TNO-6 (1.5 mg/kg) produced more severe kidney damage--although this was reversible--than CDDP (2 mg/kg). Half-lives of distribution were 4.0-5.1 min for TNO-6 and 9.7 min for CDDP, while half-lives of elimination were 3.6-6.6 days and 5.9 days respectively. Plasma levels, normalized for the dose, were at least two times higher after TNO-6 than after CDDP. Twelve weeks after drug administration, plasma levels were undetectable, while tissue concentrations could still be measured. The platinum concentration in kidney cortex was higher after CDDP than after TNO-6.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0277-5379
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1087-104
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Preclinical studies on toxicity, antitumour activity and pharmacokinetics of cisplatin and three recently developed derivatives.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't