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 ∼50% lower in CF patients. Tacrolimus trough concentration did not accurately predict the area under the concentration curve (AUC0–12), but the concentration measured 3 h postdose (C3) was tightly correlated with the AUC0–12 in both CF (r2= 0.86) and non-CF (r2= 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. C3 is tightly correlated with AUC0–12 in lung transplant recipients with and without CF.
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Document Type: Research Article
Departments of Chest Medicine
Clinical Chemistry, Erasme University Hospital, Brussels, Belgium
Department of Pharmacology, University Hospital, Limoges, France
Publication date: June 1, 2005