Impact of absorption profiling on efficacy and safety of cyclosporin therapy in transplant recipients

Abstract

The optimisation of cyclosporin therapy remains a challenge because of the very narrow therapeutic window and the highly variable pharmacokinetics of the drug. Therefore, there has been a concerted effort in the clinical transplant community to explore and test cyclosporin monitoring tools and techniques that will allow blood concentrations of cyclosporin to be maintained within the narrow therapeutic window in order to maximise efficacy and minimise toxicity. Absorption profiling is a simple and accurate technique for adjusting dosages of cyclosporin microemulsion that utilises an estimation of the rate and extent of cyclosporin absorption in order to optimise immunosuppression in the individual patient. Two estimation tools in particular are an abbreviated area under the concentration-time curve (AUC) for the first 4 hours postdose and a single sampling point at 2 hours postdose. These 2 monitoring strategies have not only been validated as an accurate estimation of cyclosporin bioavailability but have been demonstrated to significantly improve clinical outcomes in patients compared with traditional trough concentration monitoring. The evidence presented in this review demonstrates that absorption profiling results in the following clinical benefits compared with trough concentration monitoring: (i) reduced incidence of acute rejection; (ii) reduced severity of rejection episodes; (iii) reduced nephrotoxicity; and (iv) a rational basis for dosage adjustments. The optimisation of immunosuppressive therapy continues to be a major priority in the management of the organ transplant recipient. Absorption profiling is a sensitive and practical approach for optimising the dosage of cyclosporin microemulsion, and can further extend the benefits of cyclosporin immunosuppression in the individual patient.