IMPROVED ABSORPTION OF CYCLOSPORINE-A FROM A NEW MICROEMULSION FORMULATION - IMPLICATIONS FOR DOSAGE AND MONITORING

Recently, a new oral microemulsion formulation of cyclosporin A (CsA) - Neoral (Sandoz, Basle, Switzerland) - with a higher bioavailability has become available. Ten stable paediatric renal transplant recipient s with excessive variations in CsA trough levels with the original San dimmun (Sandoz, Basle, Switzerland) preparation were switched to Neora l on a 1:1 basis. Pharmacokinetic studies revealed impaired absorption of Sandimmun in six patients. Compared with equal doses of Sandimmun, the 8-h area under the concentration-time curve increased from 1,422 to 2,657 ng x h/ml and the peak concentration rose from 319 to 824 ng/ ml (P < 0.01). In six patients with Sandimmun malabsorption, conversio n on a 1:1 basis led to a reduction in creatinine clearance which was reversible after dose reduction by 9%-25%. With trough levels at the l ower end of the present target range, creatinine clearance stabilised around pre-conversion values.