Reduced cyclosporine absorption preceded acute allograft rejection in a child with a liver transplant

Abstract

This case report correlates impaired cyclosporine absorption from the traditional oral formulation in a 9-year-old liver transplant recipient with subsequent acute allograft rejection. Although impaired absorption in this patient was documented by cyclosporine pharmacokinetic profiling (steadystate area under the cyclosporine concentrationtime curve or AUC), no indication was evident from the pre-dose cyclosporine trough level, which was within the typical target range of blood concentrations. However, when the subject received the microemulsion formulation of cyclosporine the AUC value reflected an adequate absorption pattern. We recommend that if malabsorption is suspected in the de novo pediatric liver transplant patient, then single-sample pre-dose trough cyclosporine levels should not be relied on as an indicator of sufficient immunosuppression and that a limited sampling strategy be used to confirm or rule out impaired absorption.

Immunosuppressant drugs - the role of therapeutic drug monitoring

“…While the introduction of cyclosporin resulted in a marked improvement in graft survival, its use was not without problems. From the initial discovery of cyclosporin [22] to the present day [23], the absorption of the drug has been problematical [24]. Variable absorption and a narrow therapeutic index (the drug causes irreversible kidney damage when given in too high a dose [25]) has resulted in the measurement of cyclosporin blood concentrations so that the dose of the drug can be tailored to the patient in such a way as to maximize therapeutic ef®cacy while minimizing toxicity [26].…”