BILE-INDEPENDENT ABSORPTION OF CYCLOSPORINE FROM A MICROEMULSION FORMULATION IN LIVER-TRANSPLANT PATIENTS

A microemulsion formulation of CsA, which was anticipated to be indepe ndent of bile for oral absorption, was compared with the currently mar keted formulation in liver transplant patients with external biliary d rainage. Eleven patients aged 47.6 +/- 13.1 years and weighing 75.8 +/ - 5.7 kg received single 400-mg oral doses of each formulation in a ra ndomized, crossover protocol on days 4 and 6 after transplant. Serial venous blood samples were collected over a 12-hr period after each adm inistration and whole blood CsA concentrations were determined by a va lidated RIA specific for the parent compound. Systemic exposure to CsA was consistently higher from the microemulsion formulation in all pat ients, as judged by the peak concentration and the area under the curv e. Specifically, the area under the concentration time curve was 943 /- 400 vs. 2378 +/- 911 ng . hr/ml, indicating an average 156% higher bioavailability from the microemulsion compared with the currently mar keted formulation in liver transplant patients in the absence of bile.