Linked Life Data

1568289

Source:http://linkedlifedata.com/resource/pubmed/id/1568289

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1992-5-22
pubmed:abstractText
The influence of a commercial formulation of 5-fluorouracil (5-FU) on the stability and pharmacological properties of two platinum derivatives, cisplatin and carboplatin, was studied to determine whether the drugs could be mixed in containers or intravenous lines. When cisplatin was incubated in a French commercial formulation of 5-FU (Fluoro-uracile, Roche, France), high-performance liquid chromatographic (HPLC) studies demonstrated a rapid disappearance of the parent platinum compound, the extent of the degradation being 75% after 3.5 h. These studies also revealed that the degradation was not caused by a reaction between 5-FU and cisplatin but rather resulted from an interaction between cisplatin and trometamol, the excipient used in the French 5-FU formulation to buffer the solution at pH 8.2. The sole presence of trometamol in a cisplatin solution for 24 h at 30 degrees C resulted in the complete inhibition of both the ability of cisplatin to bind in vitro to human serum albumin and the antitumor activity of the cytostatic agent against P388 leukemia in mice (T/C% = 88% for cisplatin+trometamol vs greater than 333% for cisplatin). When cisplatin was incubated at the same pH in trometamol-free sodium hydroxide solutions (the excipient used in 5-FU formulations in several countries, including the United States and the United Kingdom), the parent compound was transformed into reactive species that were toxic to mice (T/C% = 40% in P388 leukemia). The degradation determined for a carboplatin-trometamol admixture using HPLC was similar to that found for cisplatin but occurred at a slower rate (0 after 3.5 h incubation and 55% after 24 h). The antitumor activity of carboplatin in P388-bearing mice was not significantly altered by a 24-h period of preincubation in the presence of trometamol (T/C% = 209% vs 241% for treatment with carboplatin in the absence of trometamol). As in the case of cisplatin, incubation of carboplatin for 24 h in a sodium hydroxide solution resulted in a toxic effect (T/C% = 64%). Our results thus demonstrate the incompatibility of both cisplatin and carboplatin with commercial formulations of 5-FU.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
461-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:1568289-Animals, pubmed-meshheading:1568289-Antineoplastic Agents, pubmed-meshheading:1568289-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:1568289-Carboplatin, pubmed-meshheading:1568289-Chemistry, Pharmaceutical, pubmed-meshheading:1568289-Chemistry, Physical, pubmed-meshheading:1568289-Chromatography, High Pressure Liquid, pubmed-meshheading:1568289-Cisplatin, pubmed-meshheading:1568289-Drug Stability, pubmed-meshheading:1568289-Excipients, pubmed-meshheading:1568289-Fluorouracil, pubmed-meshheading:1568289-Leukemia P388, pubmed-meshheading:1568289-Mice, pubmed-meshheading:1568289-Mice, Inbred DBA, pubmed-meshheading:1568289-Organoplatinum Compounds, pubmed-meshheading:1568289-Physicochemical Phenomena, pubmed-meshheading:1568289-Serum Albumin, pubmed-meshheading:1568289-Time Factors
pubmed:year
1992
pubmed:articleTitle
Modification of the physicochemical and pharmacological properties of anticancer platinum compounds by commercial 5-fluorouracil formulations: a comparative study using cisplatin and carboplatin.
pubmed:affiliation
Laboratoire de Pharmacodynamie Clinique, Centre Oscar Lambret, Lille, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't