Therapeutic Drug Monitoring of Prednisolone After Lung Transplantation

Abstract

Background: Despite well-known and serious potential side-effects of corticosteroid therapy, therapeutic drug monitoring (TDM) of prednisolone is rarely performed after lung transplantation (LTx). Methods: We measured prednisolone exposure using a 6-hour area-under-the-curve (AUC) analysis in 52 LTx recipients (41 bilateral, 9 single and 2 heart-lung), who were 99 ± 13 (mean ± SEM) weeks (range 4 to 380) post-LTx. Fourteen of 52 had cystic fibrosis (CF), and 36 of 52 were on cyclosporine and 16 of 52 on tacrolimus. Prednisolone dose was 9.8 ± 0.7 mg/day (range 1 to 20). Results: Only 9 of 52 LTx patients had a prednisolone AUC within the previously reported reference range for healthy adult control subjects (170 to 260 nmol.hr/liter/milligram prednisolone). Six patients had values below and 37 above this range. Prednisolone AUC was higher in patients with CF compared with non-CF patients (511 ± 82 vs 349 ± 27 nmol.hr/liter/milligram, p < 0.02) and 70% of LTx recipients had measurable prednisolone levels at baseline (26.5 ± 4.5 nmol/liter), unlike normal controls. Conclusions: LTx recipients show a wide inter-individual variation in prednisolone pharmacokinetics; therefore, many are overdosed on conventional protocols. Side-effects of corticosteroid therapy remain a major clinical problem after transplantation, justifying the use of prednisolone TDM to optimize dosing and minimize morbidity. Show more