ArticleBritish journal of pharmacology1996
Metabolism of the macrolide immunosuppressant, tacrolimus, by the pig gut mucosa in the Ussing chamber.
Article in British journal of pharmacology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 75 citations in OpenAlex.
- Multidrug resistance-associated protein 2 (MRP2/ABCC2) haplotypes significantly affect the pharmacokinetics of tacrolimus in kidney transplant recipients.Clinical pharmacokinetics · 2013Trial
- Gutsy science: In vitro systems of the human intestine to model oral drug disposition.Pharmacology & therapeutics · 2022Review
- Drug Transport across Porcine Intestine Using an Ussing Chamber System: Regional Differences and the Effect of P-Glycoprotein and CYP3A4 Activity on Drug Absorption.Pharmaceutics · 2019Article
- Influence of tacrolimus metabolism rate on renal function after solid organ transplantation.World journal of transplantation · 2017Review
- Multigene predictors of tacrolimus exposure in kidney transplant recipients.Pharmacogenomics · 2015Article
- Explaining variability in ciclosporin exposure in adult kidney transplant recipients.European journal of clinical pharmacology · 2010Article
- Tacrolimus nephrotoxicity: beware of the association of diarrhea, drug interaction and pharmacogenetics.Pediatric nephrology (Berlin, Germany) · 2010Article
- Clinical pharmacokinetics and pharmacodynamics of tacrolimus in solid organ transplantation.Clinical pharmacokinetics · 2004Review
- Mechanisms of clinically relevant drug interactions associated with tacrolimus.Clinical pharmacokinetics · 2002Review
- Active transport of the angiotensin-II antagonist losartan and its main metabolite EXP 3174 across MDCK-MDR1 and caco-2 cell monolayers.British journal of pharmacology · 2000Article
- Primary porcine enterocyte and hepatocyte cultures to study drug oxidation reactions.British journal of pharmacology · 2000Article
- Effects of intestinal and hepatic metabolism on the bioavailability of tacrolimus in rats.Pharmaceutical research · 1998Article
- Pharmacokinetics of mycophenolic acid, tacrolimus and sirolimus after gastric bypass surgery in end-stage renal disease and transplant patients: a pilot study.Clinical transplantationArticle
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1. The macrolide tacrolimus (FK506), used as an immunosuppressant, is a cytochrome P450 (CYP) 3A substrate in the liver. The metabolism of tacrolimus and the transport of its metabolites in the pig gut was studied in the Ussing chamber. Tacrolimus and its metabolites were quantified by h.p.l.c./mass spectrometry. 2. In the Ussing chamber, demethyl, didemethyl, hydroxy and hydroxy-demethyl tacrolimus were generated. Their formation was concentration- and time-dependent. The metabolite pattern was not different from that after incubation of tacrolimus with human small intestinal microsomes. 3. The metabolite formation was highest in the duodenum and declined in the order duodenum > jejunum > ileum > colon > stomach. 4. Since tacrolimus metabolism was inhibited by the specific CYP3A inhibitors, troleandomycin and ketoconazole, we concluded that these enzymes are involved in intestinal metabolism of tacrolimus. 5. Tacrolimus metabolites re-entered the mucosa chamber (> 90%) and passed through the small intestinal preparation into the serosa chamber. 6. It is concluded that tacrolimus is metabolized in the intestine, that the metabolites are able to re-enter the gut lumen and also enter into the portal vein and that small intestinal metabolism and transport is at least in part responsible for the low oral bioavailability of tacrolimus.
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