PHARMACOKINETICS OF AN ORAL SOLUTION OF THE MICROEMULSION FORMULATIONOF CYCLOSPORINE IN MAINTENANCE PEDIATRIC LIVER-TRANSPLANT RECIPIENTS

Background. A comparison of the oral bioavailability of cyclosporine f rom the original formulation (CsA) and from the new formulation, cyclo sporine for microemulsion (CsA-ME), was made in pediatric maintenance liver transplant patients within two age groups (group 1, ages 1-5 yea rs; group 2, ages 6-17 years) in an open-label, multicenter, randomize d crossover trial, All patients were at least 6 months past transplant ation and were receiving CsA maintenance therapy. Methods. In study pe riod 1 (days 1 through 14), patients were administered either CsA or C sA-ME at the same b.i.d. dosage as their maintenance therapy. Upon ent ry into period 2 (days 15 through 28), patients were converted to the alternate formulation at a 1:1 mg dose ratio, On day 29, all patients returned to the CsA treatment administered at study entry, with follow -up on day 35. Dosage adjustments were not allowed with either CsA or CsA-ME. Twelve-hour pharmacokinetic profiling was performed at the end of periods 1 and 2. Results. Both the mean area under the concentrati on-versus-time curve and the mean maximum blood concentration of cyclo sporine-both normalized for dose-were significantly increased: by 66% and 109%, respectively, in patients receiving CsA-ME compared with tho se receiving CsA in group 1 and by 39% and 75%, respectively, in group 2. During this study, liver function remained stable, and serum creat inine and blood pressure did not differ significantly between treatmen t groups. Conclusions. This study shows increased bioavailability in a ll patients converted to CsA-ME, with the greatest increase seen in pa tients with the lowest initial cyclosporine bioavailability. The toler ability was similar between the two formulations during this study.