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Alterations of cyclosporin A metabolism induced by mycophenolate mofetil

L Pape1, K Froede, J Strehlau

  • 1Department of Pediatric Nephrology, Medical School of Hannover, Carl-Neuberg-Strasse 1, D-30627 Hannover, Germany. larspape@t-online.de

Pediatric Transplantation
|August 2, 2003
PubMed

Insights

Mycophenolate mofetil (MMF) may alter cyclosporine (CsA) metabolism in pediatric transplant patients. Lower CsA levels observed with MMF suggest potential adjustments in dosing or therapeutic targets are needed.

Area of Science:

  • Pharmacology
  • Immunosuppression
  • Pediatric Transplantation

Background:

  • Cyclosporine (CsA) is a key immunosuppressant in organ transplantation.
  • Mycophenolate mofetil (MMF) is frequently added to CsA-based immunosuppression regimens.
  • Observed lower CsA 2-hour post-dose levels (C2) in patients receiving MMF prompted this investigation.

Purpose of the Study:

  • To investigate potential differences in CsA metabolism when MMF is co-administered.
  • To evaluate the impact of MMF on CsA pharmacokinetic profiles in pediatric transplant recipients.

Main Methods:

  • A comparative study involving pediatric patients receiving CsA with or without MMF.
  • Measurement of CsA C0 and C2 levels in 48 patients.
  • Full area under the curve (AUC) determination in 11 patients.
  • Statistical analysis to compare CsA levels and correlate C2 with AUC.

Main Results:

  • Significantly lower C2 levels were observed in patients treated with MMF (617 +/- 230 ng/mL) compared to those without MMF (750 +/- 271 ng/mL) at similar CsA dosages (p < 0.05).
  • CsA C2 levels demonstrated a strong correlation with AUC (r = 0.95).
  • A novel, safer equation (AUC = 139 + 6.17 x C2) was derived for C2-limited sampling strategy.

Conclusions:

  • MMF appears to alter CsA metabolism in pediatric transplant recipients.
  • Current therapeutic target values for CsA may need adjustment when MMF is used concurrently.
  • Higher CsA doses might be required to achieve therapeutic efficacy in patients on MMF combination therapy.

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