Linked Life Data

10623492

Source:http://linkedlifedata.com/resource/pubmed/id/10623492

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-3-21
pubmed:abstractText
Plasma pharmacokinetics, excretion balance and urinary metabolites of methoxymorpholino doxorubicin (MMDX) were investigated in male and female rats and in female dogs after i.v. administration of the(14)C-labelled drug. The mean total recovery of radioactivity in 96 h (urine plus faeces) was approximately 74 and 60% dose in male and female rats, respectively, while in female dogs approximately 72% dose was recovered in 336 h. Most of the radioactivity was present in faeces, with the urinary elimination accounting for only 3-4% dose in rats and dogs. These data suggest that biliary excretion is an important route of elimination of MMDX and/or its metabolites in both species. No differences were observed in the urinary metabolic profile of male and female rats. Two main peaks were present in radiochromatograms of urine from rats and dogs, i.e. MMDX and its 13-dihydro metabolite (MMDX-ol), accounting for approximately 25 and 20% of total radioactivity in 0-24-h urine in rats and 30 and 36% in dogs. The MMDX-ol/MMDX ratio in dog urine was higher than that observed in rat urine. No aglycones were detected in the urine samples from either species. In the rat, the plasma concentration-time profile suggested that the disposition of MMDX, MMDX-ol and total radioactivity is not sex-dependent. MMDX was the major species present in the systemic circulation; its AUC (0-96 h) accounted for 70% of total plasma radioactivity with the sum of AUC (MMDX) plus AUC (MMDX-ol) accounting for 77% of total radioactivity. In the dog, the sum of AUC (MMDX) plus AUC (MMDX-ol) amounted to 8% of radioactivity AUC(0-t(z) indicating that an important proportion of other(s) unknown metabolite(s) is present in dog plasma. Plasma levels of MMDX-ol in the rat were approximately 10-fold lower than those of the parent compound, whereas they were three times higher than those of MMDX in the dog. These data show that the reduction of the 13-keto group of MMDX is species-dependent, and occurs preferentially in the dog compared to the rat.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1043-6618
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
239-48
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Species-differences in disposition and reductive metabolism of methoxymorpholinodoxorubicin (PNU 152243), a new potential anticancer agent.
pubmed:affiliation
Drug Metabolism Research, Pharmacia and Upjohn, Viale Pasteur 10, Nerviano, Milan, 20014, Italy.
pubmed:publicationType
Journal Article, Comparative Study