Severe elevations of FK506 blood concentration due to diarrhea in renal transplant recipients

Clinical Transplantation
Koichiro SatoHajime Okazaki

Abstract

The rate of metabolism in the intestine of oral administered FK506 decreases as FK506 passes on to the lower intestine. In transplant recipients with diarrhea given oral FK506, the main areas for absorption of FK506 shift to the lower intestine, where the ability to metabolize FK506 is weaker. Therefore it is considered likely that when FK506 is administered to recipients with diarrhea, the blood concentration of FK506 will be higher. Twenty recipients experiencing episodes of diarrhea were investigated to determine the trough level of FK506 and the time required for the FK506 trough level to return to the level that obtained before diarrhea. AUC0-4h and Cmax of FK506 were investigated in eight recipients. In cases with severe diarrhea, the daily fluctuations of FK506 blood concentration were also investigated. The FK506 trough level (p < 0.0001), AUC (p = 0.0173), and Cmax (p = 0.0173) were found to be significantly higher during episodes of diarrhea. In almost all cases, it took between 2 and 4 wk for the elevated FK506 trough level to return to its previous level following a bout of diarrhea. In the daily fluctuations of FK506 concentration, Tmax was prolonged. In some cases, the concentration was highest just before adminis...Continue Reading

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Citations

Jan 22, 2010·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Sandrine LeroyTim Ulinski
May 15, 2010·The Tohoku Journal of Experimental Medicine·Ikuo TakedaSusumu Satomi
Jun 5, 2014·Current Infectious Disease Reports·Carolyn D Alonso, Mini Kamboj
Apr 8, 2010·Pediatric Clinics of North America·Simon UrschelLori J West
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Dec 12, 2012·Expert Opinion on Pharmacotherapy·Thomas Rath
Jul 23, 2016·Clinical Transplantation·Susanne BrakemeierKlemens Budde
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Feb 15, 2019·European Journal of Clinical Pharmacology·Ruth RahamimovBenaya Rozen-Zvi
Dec 28, 2016·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Benaya Rozen-ZviRuth Rahamimov
Jul 30, 2020·Expert Opinion on Drug Metabolism & Toxicology·Alexandra L DegraeveLaure Elens
Jul 14, 2020·Pharmacology & Therapeutics·Françoise Stanke-LabesqueUNKNOWN French Society of Pharmacology and Therapeutics
Nov 2, 2020·Thérapie·Anaëlle ChavantFrançoise Stanke-Labesque

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