IngentaConnect Severe elevations of FK506 blood concentration due to diarrhea in...

Authors: Koichiro Sato¹; Noritoshi Amada²; Takaomi Sato²; Shunji Miura²; Yoichi Ohashi³; Satoshi Sekiguchi¹; Susumu Satomi¹; Hajime Okazaki³

Source: Clinical Transplantation, Volume 18, Number 5, October 2004 , pp. 585-590(6)

Publisher: Blackwell Publishing

Abstract:

Sato K, Amada N, Sato T, Miura S, Ohashi Y, Sekiguchi S, Satomi S, Okazaki H. Severe elevations of FK506 blood concentration due to diarrhea in renal transplant recipients.

Clin Transplant 2004 DOI: 10.1111/j.1399-0012.2004.00232.x © Blackwell Munksgaard, 2004 Abstract: Background:

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. Material and Methods:

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. AUC_0-4h and C_max of FK506 were investigated in eight recipients. In cases with severe diarrhea, the daily fluctuations of FK506 blood concentration were also investigated. Result:

The FK506 trough level (p < 0.0001), AUC (p = 0.0173), and C_max (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, T_max was prolonged. In some cases, the concentration was highest just before administration of FK506, when it should have been at trough level. Conclusions:

Diarrhea caused significant elevations of trough level, AUC_0-4h and C_max of FK506, and the prolongation of T_max in renal transplant recipients administered FK506.

Keywords: area under the concentration–time curve; diarrhea; FK506; trough level

Document Type: Research article

DOI: 10.1111/j.1399-0012.2004.00232.x

Affiliations: 1: Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai 2: Department of Surgery, Sendai Shakaihoken Hospital, Sendai 3: Department of Surgery, Koritu Katta Sogo Hospital, Shiroishi, Japan

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