Linked Life Data

3308482

Source:http://linkedlifedata.com/resource/pubmed/id/3308482

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1987-11-20
pubmed:abstractText
A toxicology study of cis-diamminedichloroplatinum (II) (CDDP), aqua(1,1-bis-(aminomethyl)cyclohexane)sulfatoplatinum(II) (TNO-6), diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA), cis-dichloro-trans-dihydroxo-cis-bis(isopropylamine)platinum-(IV) (CHIP) and ethylenediaminemalonatoplatinum(II) (JM-40) was carried out in dogs. The main purpose of the study was to compare the results with those obtained earlier in mice and rats and with the toxicology data in humans. Each platinum compound was tested in three dogs. Each dog received three intravenous bolus injections at intervals of 3 weeks. The compounds were administered in dosages of 1.2, 1.0, 12, 10 (or 6) and 10 mg/kg, respectively. Toxic death occurred for two dogs (both on day 54) from haematotoxicity (10 mg/kg CHIP) and renal toxicity (TNO-6), respectively. Serum urea nitrogen and creatinine concentrations were variable after TNO-6 and remained within normal values after treatment with the other compounds. Severe proteinuria was observed in all three dogs treated with TNO-6. Values returned to normal within 16 days. JM-40 did not cause significant proteinuria. CDDP, CBDCA and CHIP caused short-lasting and slight proteinuria. CHIP caused a severe reduction in the number of leukocytes and platelets, while the other drugs caused acceptable reductions. Except after the high dose CHIP regimen, haematotoxicity was of a transient nature. Vomiting in order of severity occurred after TNO-6, CHIP, CDDP and JM-40, while CBDCA did not cause any vomiting. The dogs were sacrificed 6 weeks after the last drug dose. Organs were fixed for histopathology to complete and support clinical-toxicological parameters. On the basis of the results from the single-dose study in dogs and those obtained earlier in mice and rats it can be concluded that the gain from the use of the dog as a prognosticator for organ toxicity in man was disappointing and limited to the prediction of vomiting.
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
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1147-54
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Preclinical toxicology of platinum analogues in dogs.
pubmed:affiliation
Radiobiological Institute TNO, Rijswijk, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't