Sevelamer and pharmacokinetics of cyclosporin A after kidney transplantation

Sir,

In their interesting article, Pieper et al. analysed prospectively the effect of sevelamer on the pharmacokinetics of cyclosporin (CsA) and mycophenolate mofetil (MMF) in kidney transplanted patients [1]. They provide the reassuring message that, in contrast to MMF, CsA kinetics are not significantly modified by the intake of sevelamer. These results are in sharp contrast to the observation and potential mechanisms that we reported recently [2,3].

The short duration (4 days) and limited statistical power (10 adults and eight children) of the study of Pieper et al. make such a strong message rather questionable [4]. Indeed, only 4 days after starting sevelamer, none of the CsA parameters (measured by Cedia and FPIA assays) was completely stable: the area under the curve (AUC) decreased from 3547±660 to 3230±612 ng/h/ml, Cmax decreased from 955±193 to 855±272 ng/ml and Tmax increased from 1.3 to 1.5 h. In addition, when measured with polyclonal antibodies, the CsA levels decreased significantly and, among its primary metabolites determined by HPLC, the AUC and Cmax of AM1—which also has an immunosuppressive action [5]—decreased significantly by 30 and 25%, respectively.

Despite these observations, the authors conclude that ‘sevelamer intake for several days does not significantly influence CsA kinetics’. Based on their data, this conclusion appears at least premature, especially if the risk of transplant rejection due to insufficient immunosuppression is considered [6]. Great caution in the use of sevelamer in transplanted patients is still warranted until a careful long-term, large size study on the potential interaction of sevelamer with CsA solves the question.

Conflict of interest statement. None declared.

Dominik Uehlinger1, Hans-Peter Marti2, Michel Jadoul3 and Jean-Pierre Wauters1

1 Division of Nephrology-Hypertension University Hospital Bern2 Division of Nephrology University Hospital Zurich Switzerland3 Division of Nephrology Cliniques Universitaires Saint-Luc Brussels Belgium Email: jean-pierre.wauters{at}insel.ch

References

  1. Pieper AK, Buhle F, Bauer S et al. The effect of sevelamer on the pharmacokinetics of cyclosporin A and mycophenolate mofetil after renal transplantation. Nephrol Dial Transplant 2004; 19: 2630–2633[Abstract/Free Full Text]
  2. Guillen-Anaya MA, Jadoul M. Drug interaction between sevelamer and cyclosporin. Nephrol Dial Transplant 2004; 19: 515[Free Full Text]
  3. Wauters JP, Uehlinger D, Marti HP. Drug interaction between sevelamer and cyclosporin. Nephrol Dial Transplant 2004; 19: 1939–1940[Free Full Text]
  4. Felipe CR, Silva HT, Pinheiro Machado PG, Garcia R, da Silva Moreira SR, Medina Pestana JO. Time-dependent changes in cyclosporine exposure: implications for achieving target concentrations. Transplant Int 2003; 16: 494–503[CrossRef][ISI][Medline]
  5. Copeland KR, Yatscoff RW, McKenna RM. Immunosuppressive activity of cyclosporine metabolites compared and characterized by mass spectrometry and nuclear magnetic resonance. Clin Chem 1990; 36: 225–229[Abstract/Free Full Text]
  6. Waiser J, Slowinski T, Brinker-Paschke A et al. Impact of the variability of cyclosporin A trough levels on long-term renal allograft function. Nephrol Dial Transplant 2002; 17: 1310–1317[Abstract/Free Full Text]




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