Improved absorption of cyclosporin A from a new microemulsion formulation: implications for dosage and monitoring

Abstract

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 recipients with excessive variations in CsA trough levels with the original Sandimmun (Sandoz, Basle, Switzerland) preparation were switched to Neoral 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×h/ml and the peak concentration rose from 319 to 824 ng/ml (P<0.01). In six patients with Sandimmun malabsorption, conversion 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 lower end of the present target range, creatinine clearance stabilised around pre-conversion values.