Tacrolimus pharmacokinetics and dose monitoring after lung transplantation for cystic fibrosis and other conditions.
In cystic fibrosis (CF), absorption of tacrolimus through the gastrointestinal tract may be impaired due to fat malabsorption. The aim of this pilot study was to compare tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure in stable lung transplant recipients with and without CF, and to determine the best single-time predictors of exposure. The study included 11 lung transplant recipients with CF and 11 without CF who received tacrolimus twice daily. Blood samples were obtained predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 h postdose on 3 separate days within 1 week. Tacrolimus pharmacokinetics and inter- and intrasubject variability of exposure were similar in the two groups, though exposure-per-milligram-dose was approximately 50% lower in CF patients. Tacrolimus trough concentration did not accurately predict the area under the concentration curve (AUC(0-12)), but the concentration measured 3 h postdose (C(3)) was tightly correlated with the AUC(0-12) in both CF (r(2)= 0.86) and non-CF (r(2)= 0.92) patients. In summary, patients with CF have a higher tacrolimus oral clearance, but nonsignificant differences in short-term inter- and intrasubject variability of exposure compared to patients without CF. C(3) is tightly correlated with AUC(0-12) in lung transplant recipients with and without CF.
Knoop
Christiane
C
Department of Chest Medicine, Erasme University Hospital, Brussels, Belgium.
Thiry
Philippe
P
Saint-Marcoux
Franck
F
Rousseau
Annick
A
Marquet
Pierre
P
Estenne
Marc
M
D000328:Adult; D019540:Area Under Curve; D003550:Cystic Fibrosis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics*
D007166:Immunosuppressive Agents; D016559:Tacrolimus