title: Severe elevations of FK506 blood concentration due to diarrhea in renal transplant recipients.
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.
  
  
  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. 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.
  
  
  RESULTS
  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 administration of FK506, when it should have been at trough level.
  
  
  CONCLUSIONS
  Diarrhea caused significant elevations of trough level, AUC0-4h and Cmax of FK506, and the prolongation of Tmax in renal transplant recipients administered FK506.
authors.affiliation: Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan. ksato@mtd.biglobe.ne.jp
authors.forename: Koichiro
authors.initials: K
authors.lastname: Sato
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Amada
authors.forename: Takaomi
authors.initials: T
authors.lastname: Sato
authors.forename: Shunji
authors.initials: S
authors.lastname: Miura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sekiguchi
authors.forename: Susumu
authors.initials: S
authors.lastname: Satomi
authors.forename: Hajime
authors.initials: H
authors.lastname: Okazaki
mesh_terms: D000284:Administration, Oral; D019540:Area Under Curve; D002940:Circadian Rhythm; D003404:Creatinine / Q000097:blood; D003967:Diarrhea / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D007408:Intestinal Absorption / Q000502:physiology; D016030:Kidney Transplantation / Q000502:physiology; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D016559:Tacrolimus