Document Detail


Disposition, metabolism, and excretion of the anticancer agent crisnatol in the rat.
MedLine Citation:
PMID:  1676660     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Disposition and metabolism of crisnatol (14C-labeled), a novel antitumor agent, was examined after po and iv administration to rats. After both routes of drug administration, there was rapid elimination of the administered radioactivity in the urine (6-12% of the dose) and feces (81-92% of the dose). The drug appeared to be rapidly absorbed after oral dose and there was substantial "first-pass" metabolism. Analysis of the excreta indicated extensive metabolism of crisnatol by the rat, with the intact compound being the major radiolabeled component in the feces (17-20% of dose). Intact drug was not present in urine. Biotransformation of crisnatol by the rat mainly involves oxidation and conjugation pathways. Hydroxylation and dihydrodiol formation in the chrysene ring and oxidation of the propanediol side chain resulted in the formation of the three major fecal metabolites. The principal metabolite in the urine was also a dihydrodiol. Concentrations of intact drug in each tissue assayed exceeded those in plasma, and in the lungs the tissue/plasma ratio approached 300 and 82 at 2 hr after iv and po doses, respectively.
Authors:
D K Patel; J L Woolley; J P Shcokcor; R L Johnson; L C Taylor; C W Sigel
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  19     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:    1991 Mar-Apr
Date Detail:
Created Date:  1991-08-14     Completed Date:  1991-08-14     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  491-7     Citation Subset:  IM    
Affiliation:
Division of Pharmacokinetics and Drug Metabolism, Wellcome Research Laboratories, Research Triangle Park, NC 27709.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / metabolism,  pharmacokinetics*,  urine
Biotransformation
Chromatography, High Pressure Liquid
Chrysenes / metabolism,  pharmacokinetics*,  urine
Feces / chemistry
Hydrolysis
Magnetic Resonance Spectroscopy
Male
Propylene Glycols / metabolism,  pharmacokinetics*,  urine
Rats
Rats, Inbred Strains
Tissue Distribution
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Chrysenes; 0/Propylene Glycols; 96389-68-3/crisnatol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Potential error in the measurement of tissue to blood distribution coefficients in physiological pha...
Next Document:  Drug metabolizing enzyme changes after chronic buthionine sulfoximine exposure modify acetaminophen ...