Linked Life Data

2828072

Source:http://linkedlifedata.com/resource/pubmed/id/2828072

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1988-3-23
pubmed:abstractText
Twelve patients were treated with high-dose etoposide give alone or in combination with cisplatin during a clinical trial. We had previously observed, in some subjects who received a combination of high-dose etoposide (350 mg/m2/day X 5 days) and cisplatin (40 mg/m2/day X 5 days), delayed hematological recovery after autologous bone marrow transplantation. Therefore we investigated the pharmacokinetics of etoposide and did not find any drug interaction with cisplatin. In four of these patients we also monitored etoposide salivary excretion and found saliva to plasma ratios in the range 0.003-0.25. The secretion of etoposide into saliva may be of concern if we consider that peroxidases in salivary glands are able to oxidize the drug leading to free radicals. In vitro experiments showed that sulfhydryl compounds are able to inhibit the formation of the etoposide radical. Furthermore, we were able to detect the presence of a new biotransformation product of etoposide in plasma samples of some patients. Fast atom bombardment liquid chromatography-mass spectrometry allowed us to identify this metabolite as the etoposide aglycone. The presence of this derivative in plasma 48 h after the last injection prompted us to delay autologous bone marrow transplantation to 72 h after the end of treatment, since the aglycone is cytotoxic and able to induce DNA strand breaks mediated by topoisomerase II.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0277-5379
pubmed:author
pubmed:issnType
Print
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1627-32
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
Clinical pharmacology of high-dose etoposide associated with cisplatin. Pharmacokinetic and metabolic studies.
pubmed:affiliation
Service de Pharmacologie Clinique (UA147 CNRS, U140 INSERM), Villejuif, France.
pubmed:publicationType
Journal Article, Clinical Trial, Controlled Clinical Trial, Research Support, Non-U.S. Gov't