COMPARISON OF CONVENTIONAL ORAL CYCLOSPORINE AND CYCLOSPORINE MICROEMULSION FORMULATIONS IN CHILDREN WITH A LIVER-TRANSPLANT

We studied 22 children (mean age: 8.42 years, range: 1.9-15.6 years) w ith a liver transplant to compare the pharmacokinetics of oral cyclosp orine (CsA) microemulsion to the conventional formulation, The CsA tre atment (mean dose: 5.9 mg/kg/day, range: 3.0-11.7 mg/kg/day) was conve rted 1:1 on a milligram-to-milligram basis to the microemulsion formul ation, Five days after the conversion, the mean peak blood CsA concent ration was higher (microemulsion: 963 ng/ml, range: 518-1864 ng/ml; co nventional: 431 ng/ml, range: 98-888 ng/ml; P<0.0001) and it was reach ed faster (median time of peak concentration: 1.6 hr vs, 2.9 hr, range : 1.0-3.0 hr vs, 1.9-4.0 hr; P=0,0009), The absorption lasted on the a verage 19% longer after the conventional formulation, The area under t he concentration versus time curve (AUG) was larger after the microemu lsion formulation in all but one patient (P=0,001) by a mean factor of 1.80 (range: 0.72-3.04), The trough CsA level after the microemulsion formulation was more closely related to peak concentration (r(2)=0.86 vs, 0.45) and AUC (r(2)=0.84 vs. 0,47); thus, therapeutic drug monito ring may be more useful, After 6 months on the new formulation, the re sults for the whole group were similar, but in five children the AUC w as comparable to the AUC obtained with the conventional formulation, N o rejections occurred, and the liver and kidney functions remained unc hanged, A 1:1 conversion can be safely performed in children, based on a B-month follow-up, However, the total drug exposure changes in sign ificant ways, which, on a long-term basis, may improve the immunosuppr ession in an underimmunosuppressed patient, but may increase the risk for dose-related adverse effects in others.