Background Therapeutic monitoring of everolimus is necessary to determine an optimal dosage regimen in lung transplantation patients to prevent graft rejection due to the narrow therapeutic window. The area under the concentration-time curve (AUC–12) is the best strategy for pharmacokinetic study because it reflects total drug exposure in the body, especially in cystic fibrosis (CF) patients who have abnormalities in the gastrointestinal system.
Purpose The aim of this study was to evaluate the absorption profile of everolimus in patients with CF after lung transplantation in order to optimise immunosuppressive therapy.
Material and methods A pharmacokinetic, descriptive and cross sectional study was conducted in lung transplant patients with determination of AUC–12 of everolimus at less than 4 months post-transplantation. All patients were taking combined immunosuppressive treatment with everolimus. After a minimum of 7 days of receiving the same dose, nine blood samples were collected at predose, and at 0.5, 1, 2, 3, 4, 6, 8 and 12 h post-morning dose. Everolimus concentrations were measured by QMS immunoassay.
Results 7 full pharmacokinetic analyses were performed in bilateral lung transplant patients. All were women with a median age of 26 years (range 13–40) and median weight of 47 kg (range 28–67). A Cmax of 6.40 ng/mL (range 5.64–18.51) was reached at 2 h (range 1–6). When target trough levels were achieved (3–8 ng/mL), median everolimus exposure was 53.10 ng.h/mL (range 30.81–113.31). Two patients showed a normal absorption profile of everolimus and 5 patients showed a low overall exposure to everolimus because the value Cmin and AUC were below the normal range. All patients underwent dose/interval modification of everolimus after the results. Following adjustments, all patients reached levels within the therapeutic range.
Conclusion The pharmacokinetic variability of everolimus is very high. Monitoring everolimus levels could optimise immunosuppressive therapy. The AUC can be calculated in any CF patient regardless of the time after transplantation as long as they do not have trough levels in the therapeutic range.
No conflict of interest.
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