Evaluation of increased bioavailability of tacrolimus in rats with experimental renal dysfunction

The effects of renal failure on the hepatic and intestinal extraction of tacrolimus were evaluated to examine the mechanisms for the increased bioavailability of this drug in cisplatin‐induced renal failure model rats. Tacrolimus extractions in the liver and intestine were evaluated by intravenous,...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmacy and pharmacology 2002-01, Vol.54 (1), p.65-70
Main Authors: Okabe, Hiromi, Yano, Ikuko, Hashimoto, Yukiya, Saito, Hideyuki, Inui, Ken-ichi
Format: Article
Language:English
Subjects:
Acute Kidney Injury - chemically induced
Acute Kidney Injury - metabolism
Animals
Antineoplastic Agents - toxicity
Biological and medical sciences
Biological Availability
Cisplatin - toxicity
Immunomodulators
Immunosuppressive Agents - pharmacokinetics
Intestinal Absorption
Intestinal Mucosa - metabolism
Liver - metabolism
Male
Medical sciences
Pharmacology. Drug treatments
Rats
Rats, Wistar
Tacrolimus - pharmacokinetics
Tissue Distribution
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The effects of renal failure on the hepatic and intestinal extraction of tacrolimus were evaluated to examine the mechanisms for the increased bioavailability of this drug in cisplatin‐induced renal failure model rats. Tacrolimus extractions in the liver and intestine were evaluated by intravenous, intraportal and intraintestinal infusion. The intestinal metabolism and absorption rate were estimated by incubating the isolated intestine with drug solution and by an in situ loop method, respectively. Blood concentrations of tacrolimus following the intraintestinal infusion were significantly increased in rats with renal failure compared with those in normal rats. The blood concentration of tacrolimus during intraportal infusion in rats with renal failure showed non‐linearity against dose, and was increased as compared with that in normal rats. The intestinal metabolism was not altered, but the absorption rate was significantly increased in the intestine from rats with renal dysfunction. These results suggest that the hepatic metabolism of tacrolimus is impaired in rats with renal failure, and that the accelerated absorption rate in the intestine in renal dysfunction is followed by partial saturation of hepatic extraction, which may be one of the mechanisms of increased bioavailability of tacrolimus.
ISSN:0022-3573
2042-7158
DOI:10.1211/0022357021771931