Comparison of cyclosporin pharmacokinetics and dose monitoring after lung transplantation for cystic fibrosis and for other conditions

Abstract

In cystic fibrosis (CF) absorption of cyclosporine (CsA) through the gastrointestinal tract is commonly impaired due to fat malabsorption. The aim of this study was to compare the steady-state pharmacokinetics of CsA and the inter- and intra-subject variability of CsA exposure, and to determine the best single-time predictors of the Area Under the Curve (AUC) in stable lung transplant recipients with (n=10) and without (n=10) CF. All patients received Neoral twice-daily. Blood samples were obtained predose and at 0.5,1,1.5,2,2.5, 3,4,5,8,12 h postdose on 3 separate days within a 5-day period. CsA exposure and pharmacokinetics variables were similar in the 2 groups, though exposure-per-milligram-dose was 25% lower in the CF patients. Coefficients of inter-subject variability were numerically higher in CF patients, but the difference between groups did not reach significance. On the other hand, Cmax,C2, and AUC showed a two-fold greater intra-subject variablility in the CF patients. CsA trough concentration did not predict accurately the AUC, but C3 was the best single-point predictor of the AUC in both CF (r2=0.87) and non-CF (r2=0.82) patients. We conclude that compared to patients without CF, patients with CF show a lower bioavailibility of CsA and a greater variability of Cmax, C2, and AUC. C3 is the best single-point predictor of the AUC in lung transplant recipients with and without CF. Supported in part by a grant from Novartis Pharma Belgium.