title: Excess fluid distribution affects tacrolimus absorption in peritoneal dialysis patients.
abstract: BACKGROUND
  Excess fluid distribution is a common disorder in peritoneal dialysis (PD) patients. Tacrolimus malabsorption may also occur in PD patients, and may lead to acute allograft rejection after transplantation. The purpose of this study was to evaluate the relationship between tacrolimus pharmacokinetics and excess fluid distribution according to pre-transplant dialysis modality.
  
  
  METHODS
  We retrospectively analyzed 41 adult living-donor kidney transplantations, including nine PD patients and 32 hemodialysis (HD) patients. We examined tacrolimus pharmacokinetics in the peri-operative period and determined the association between the tacrolimus absorption rate and body weight reduction. The absorption efficacy of tacrolimus was evaluated as the dose-normalized tacrolimus absorption rate. Tacrolimus concentrations in PD effluent were measured by high-performance liquid chromatography.
  
  
  RESULTS
  The tacrolimus absorption rate on the day before kidney transplantation tended to be lower in PD patients than in HD patients; however, the rate improved after kidney transplantation and was similar in both groups of patients. The peak tacrolimus concentration time was later in PD patients than in HD patients. The body weight reduction after kidney transplantation was greater in PD patients than in HD patients, and was significantly associated with the change in tacrolimus absorption rate (p=0.04, r=0.32). Only 0.002% of the oral tacrolimus dose was removed by PD itself.
  
  
  CONCLUSIONS
  Excess fluid distribution in PD patients appears to contribute to tacrolimus malabsorption rather than PD itself. We should consider the risk of tacrolimus malabsorption in patients with possible excess fluid distribution, particularly in PD patients.
authors.affiliation: Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan. sofue@med.kagawa-u.ac.jp.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sofue
authors.affiliation: Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Inui
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kiyomoto
authors.affiliation: Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Moriwaki
authors.affiliation: Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan.
authors.forename: Taiga
authors.initials: T
authors.lastname: Hara
authors.affiliation: Department of Pharmacy, Kagawa University Hospital, Kagawa, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Pharmacy, Kagawa University Hospital, Kagawa, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Fukuoka
authors.affiliation: Shiga Pharmaceutical Association Proof Center, Kusatsu, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Banno
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.affiliation: Department of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kakehi
authors.affiliation: Division of Nephrology and Dialysis, Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kohno
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001835:Body Weight; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D016030:Kidney Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D006435:Renal Dialysis / Q000009:adverse effects; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014883:Water-Electrolyte Imbalance / Q000097:blood / Q000209:etiology / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus