Apport du Néoral® en transplantation rénale

Summary

Neoral® is a novel formulation in which cyclosporin is suspended in a uniform, fine microemulsion by a combination of lipophilic solvent, hydrophilic solvent and surfactant. Prospective randomised double-blind clinical trials have confirmed that absorption of cyclosporin is more rapid, complete and consistent from Neoral®than from previous formulations (such as Sandimmun®). Use of Neoral® for acute or maintenance immunosuppression with conventional trough concentrations has shown no evidence of long term renal or other toxicity.

The prospective, randomised multicentre pharmaco-epidemiological study performed in 1097 stable Canadian renal transplant patients under conditions of normal clinical practice has shown that patients can be safely switched from using gelatin capsules to Neoral®, and has confirmed the pharmacokinetic advantages observed in de novo use. Peak cyclosporin concentration occurred at 1.6 vs 2.8 hours and was increased by 69% (1063 vs 627 µg/L), and exposure to cyclosporin was increased by 45% (5215 vs 3579 µg/L·h). Patients who were more than 1 standard deviation below the mean of absorption when they were receiving Sandimmun® had an almost 3-fold increase in absorption when taking Neoral®, and by 90 days postconversion all poor absorbers had become good or excellent absorbers on Neoral®. The variability of drug exposure in patients receiving cyclosporin is also significantly decreased in patients receiving Neoral® and there appears to be no long term adverse consequence of switching to Neoral®.

Preliminary pharmacokinetic data suggest that the pharmacokinetic advantages of Neoral® may also translate into reduced healthcare costs, but confirmation in formal analyses is required. The current information suggests that the more complete and consistent absorption of cyclosporin provided by Neoral® offers the opportunity for precise and effective long term immunosuppression, a critical advantage in view of the emerging relationship between variable drug exposure and long term immunological injury. However, trough concentration monitoring appears inadequate to fully exploit these advantages, and the use of a simple limited sampling strategy is emerging as an important tool for predicting drug exposure.