Linked Life Data

2265456

Source:http://linkedlifedata.com/resource/pubmed/id/2265456

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1991-2-12
pubmed:abstractText
Little is known of the pharmacology of rhodamine 123 (RH-123), an agent reported to have carcinoma-selective experimental antitumor activity. Accordingly, using a high-performance liquid chromatographic assay system with fluorescence detection, we examined the plasma decay and the biliary and urinary elimination of parent drug and metabolites in female Sprague-Dawley rats receiving RH-123 at an intravenous dose (5 mg/kg) equivalent to the therapeutic dose used in murine tumor models. Following drug administration to unconscious animals, plasma levels of drug-associated fluorescence fell in a triphasic manner (t1/2 alpha, 15 min; t1/2 beta, 1 h; t1/2 gamma, 4.7 h). In plasma, unchanged drug predominated but lower levels of the deacylated metabolite rhodamine 110 (RH-110) and two unknowns were also detectable throughout the study. Drug fluorescence was recovered extensively in both urine and bile. In unconscious animals with ureteral cannulae, urinary excretion (11.4% of the dose in 6 h) occurred predominantly as unchanged RH-123 (97% of the total), with low levels of RH-110 (2.4%) and two unknowns (less than 0.6% combined) also being present. Similarly dosed conscious animals (without surgical intervention) housed in metabolic cages showed a comparable pattern of urinary excretion, with 11.9% of the drug dose being recovered in 6 h and 21.9%, by 48 h. Biliary drug elimination accounted for 8% of the delivered dose in 6 h in unconscious animals and for 11% by 36 h in conscious animals fitted with biliary cannulae. In contrast to urinary excretion, in which unchanged drug predominated, only 50% of the fluorescence recovered in bile was attributable to RH-123. The remainder was due to a number of products that were detectable throughout the study. Of these, one present at significant levels was identified as a glucuronide conjugate of RH-123, based on the liberation of parent drug when the purified metabolite was incubated with beta-glucuronidase or hydrolyzed with 1 N hydrochloric acid. Further studies with a radiolabeled form of RH-123 are necessary to establish the identity of the remaining unknowns disclosed in this work.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0344-5704
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
205-10
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
Metabolism and elimination of rhodamine 123 in the rat.
pubmed:affiliation
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.