The effect of sevelamer on the pharmacokintics of cyclosporin and mycophenolate mofetil after transplantation

Abstract

Background. After renal transplantation, patients with insufficient graft function may require phosphate binders. It is still unknown if sevelamer, a new calcium-free phosphate binder, interferes with the uptake of immunosuppressants. We studied its effects on the pharmacokinetics of cyclosporin A (CsA) and mycophenolate mofetil. Methods. We examined 10 adults and eight children with stable renal graft function and stable CsA trough levels. A 12 h pharmacokinetic profile (10 observation points) was conducted without sevelamer, after a single dose and after 4 days of treatment with it. CsA levels were measured with both a monoclonal antibody assay (CEDIA) and a polyclonal antibody assay (FPIA), mycophenolic acid (MPA) levels by EMIT assay and CsA metabolites AM1, AM9 and AM4N by a modified HPLC method. Results. Sevelamer had no significant effect on CsA kinetics [area under the curve (AUC), peak concentration (Cmax), time of Cmax]. The AUC of AM1 was decreased by 30% and Cmax, by 25% after 4 days of sevelamer intake. MPA levels were significantly reduced by a mean of 25% of the AUC (P<0.05) and by 30% of the Cmax after a single dose of sevelamer. Conclusions. A single sevelamer dose reduces the Cmax and the AUC of MPA. Its intake for several days does not significantly influence CsA kinetics. © ERA-EDTA 2004; all rights reserved.