Comparison of Neoral and Sandimmun cyclosporin A pharmacokinetic profiles in young renal transplant recipients.
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 (Cmax) of 114%, an increase in area under the curve (AUC) of 71% and the time to reach Cmax 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 (r2 = 0.833) and NEO (r2 = 0.699) and also C1.5 h for NEO (r2 = 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.
Kabasakul
S C
SC
UMDS Department of Paediatric Nephrology, Guy's Hospital, London, UK.
Clarke
M
M
Kane
H
H
Karsten
J
J
Clark
G
G
D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004655:Emulsions; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male
D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine