title: Erythroid recovery affects tacrolimus levels after engraftment during stem cell transplantation.
abstract: Tacrolimus is commonly used in stem-cell transplants (SCT) for prophylaxis of graft-versus-host disease and is continuously administered throughout transplantation. The dose of tacrolimus is frequently decreased to maintain a desired concentration during the recovery of hemocytes after engraftment. If parameters which affect tacrolimus clearance are identified, it is of clinical use to estimate concentrations and aid dosing. The objective of this study was to identify which hematologic parameters affect tacrolimus clearance. Seventeen consecutive Japanese patients with hematological malignancies who received allogeneic SCT between March 2004 and January 2007 were enrolled in this study. Their steady-state concentrations were routinely measured and standardized as the concentration/dose (C/D) ratio ((ng/mL)/(mg/kg/d)). Multivariate analysis was performed to identify which hemocyte parameters affected the C/D ratio. Of the 13 patients, gradual dose reduction was required to combat elevated tacrolimus concentrations. The mean post-engraftment C/D ratio was higher than the pre-engraftment C/D ratio in each patient. The mean C/D ratio for all patients after engraftment was 1.56-fold higher (p=0.00004, range: 1.04-3.03) than that before engraftment. The variation ratio was calculated by dividing the C/D ratio by that on the engraftment day. Multivariate analysis revealed that the reticulocyte (RET) level (×10(3) count/µL) was the sole parameter influencing this ratio, and both parameters were expressed as: Variation ratio=0.004×RET+1.0. RET recovery of patients could influence the C/D ratio and tacrolimus clearance was affected by recipient original red blood cells, but not that of transfused red blood cells.
authors.affiliation: Department of Pharmacy, Kagawa University Hospital, Kagawa, Japan. fukuoka@med.kagawa-u.ac.jp
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Fukuoka
authors.forename: Osamu
authors.initials: O
authors.lastname: Imataki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tani
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Houchi
mesh_terms: D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006403:Hematologic Tests; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D012156:Reticulocytes / Q000166:cytology; D033581:Stem Cell Transplantation; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus