Nr. 4 - 4. Quartal 1995

Conversion to a new Microemulsion Formulation of Cyclosporin A in Renal Transplant Recipients Under Six Years of Age

A. Bökenkamp, G. Offner, P. F. Hoyer, C. Feldhoff, J. Müller-Berghaus, M. Wigger, T. Neuhaus, J. Brodehl

Absorption of Cyclosporin A (CsA) from the classic Sandimmunreg. preparation (CP) is greatly influenced by concomitant food intake. Recently Sandimmun Neoralreg., a new oral microemulsion formulation (NOF) with a more predictable pattern of absorption has been introduced. Both in adults and adolescents accelerated absorption has been demonstrated with NOF. Small children are known to have higher clearance rates of CsA than adults. Some authors therefore advocate a dosage interval of 8 hours in pre-school transplant recipients.

Aim of the present study was to evaluate the need for a shortened dosage interval in children under 6 years of age after conversion from CP to NOF.

Nine stable long-term renal transplant recipients with a mean age of 4.6 +/- 1.2 years were switched from CP to NOF at a conversion ratio of 1:0.9. Mean NOF dose was 182 +/- 36 mg/sqm per day. At steady state after conversion, a 12-hour pharmacokinetic profile of CsA was performed. CsA levels were measured in hemolyzed whole blood by monoclonal assay. Follow-up after conversion was 4.3 +/- 2.6 months.

Mean peak CsA concentration was 939 +/- 313 ng/ml, it was found 1.3 +/- 0.5 hrs post ingestion. The mean area under the concentration-time curve (AUC) was 3820 +/- 1034 ng . hr/ml and correlated with the trough level at 12 hrs (r=0.75, p < 0.05). The mean trough level was 93 +/- 35 ng/ml. Comparison with CsA profiles in 12 adolescents under NOF showed no difference in CsA concentrations at different time points post ingestion. Compared to pre-conversion, creatinine clearance estimated according to Schwartz increased slightly from 61 to 66 ml/min/1.73sqm.

Based on these findings, a modification of dosage intervals does not appear to be necessary when switching pre-school children to the NOF formulation of CsA.

Keywords:

Cyclosporin A, pharmacokinetics, renal transplantation, children, microemulsion preparation

Kurztitel:

Bökenkamp, A. et al. (1995) TxMed 4:205

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