RGD Reference Report - Pharmacokinetics of diclofenac in rats intoxicated with CCL4, and in the regenerating liver. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Pharmacokinetics of diclofenac in rats intoxicated with CCL4, and in the regenerating liver.

Authors: Reyes-Gordillo, K  Muriel, P  Castaneda-Hernandez, G  Favari, L 
Citation: Reyes-Gordillo K, etal., Biopharm Drug Dispos. 2007 Nov;28(8):415-22.
RGD ID: 2292044
Pubmed: PMID:17828713   (View Abstract at PubMed)
DOI: DOI:10.1002/bdd.569   (Journal Full-text)

The pharmacokinetics of an intravenous and oral diclofenac dose of 3.2 mg/kg was studied in male Wistar rats under control conditions, 1 and 3 days after liver damage and regeneration induced by an oral injection of CCl(4). One day after CCl(4) administration, indicators of necrosis (alanine aminotransferase), cholestasis (gamma-glutamyl transpeptidase) and regeneration (alpha-fetoprotein) were significantly increased; these effects were reversed after 3 days. In nonintoxicated rats, t(1/2) was 43.83 +/- 4.95 min, V(d) was 0.37 +/- 0.04 l/kg, Cl was 129.21 +/- 9.20 ml/min kg, AUC(i.v.) was 25.62 +/- 1.45 microg/min ml, and AUC(p.o.) was 20.21 +/- 1.03. One day after intoxication, when the liver was damaged and regenerating, the metabolism was decreased: diclofenac t(1/2) was increased to 258.21 +/- 30.80 min but V(d) did not change significantly, therefore Cl was reduced to 32.81 +/- 3.38 ml/min kg. By day 3 after intoxication, liver function, regeneration and pharmacokinetics returned to normal. The results show that liver damage and regeneration increases the bioavailability by decreasing elimination. The present observations suggest that reduction of the pharmacokinetic parameters may lead to drug accumulation in the regenerating-damaged liver with an attendant possible increase in toxic effects. The results in rats, also suggest that once hepatic injury is finished and regeneration is complete, diclofenac can be administered normally.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
animal organ regeneration  IEP 2292044 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Afp  (alpha-fetoprotein)


Additional Information