Comparison of Neoral and Sandimmun cyclosporin A pharmacokinetic profiles in young renal transplant recipients

Abstract.

A major factor influencing whole blood cyclosporin A levels in young children with renal transplants is the variable absorption of Sandimmun (SIM). Neoral (NEO) is a new microemulsion of cyclosporin A (CYA) that has been reported to have better absorption characteristics. We compared the pharmacokinetics of SIM and NEO in nine renal transplant recipients aged less than 11 years (range 4.8 – 10.9 years) and observed clinical parameters during 6 months of NEO therapy. Median CYA dosage was 149 mg/m² per day (range 98 – 226). We observed an increase in the maximum CYA concentration (C_max) of 114%, an increase in area under the curve (AUC) of 71% and the time to reach C_max was reduced from 1.75 h to 1.25 h with NEO, while 12-h trough levels (C12 h) did not change significantly. AUC correlated with C12 h for SIM (r ² = 0.833) and NEO (r ² = 0.699) and also C1.5 h for NEO (r ² = 0.775). During 24 weeks’ follow-up, the coefficient of variation of CYA levels was lower for NEO (13%) than for SIM (20%). Although CYA dosages at the start and the end of 6 months on NEO were similar, only one patient was maintained on a constant dose. Four patients had acute reversible rises in plasma creatinine which responded to a 11% reduction in NEO dose; their increase in AUC was greater than those patients not showing a rise in plasma creatinine. Overall, median plasma creatinine was unchanged at the end of the study. NEO was well tolerated by the patients; temporary nausea and headache were experienced by three patients and one of them stopped NEO after 20 days. Other biochemical parameters were not significantly different on NEO.