The effect of sevelamer on the pharmacokinetics of cyclosporin A and mycophenolate mofetil after renal transplantation.
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 (C(max)), time of C(max)]. The AUC of AM1 was decreased by 30% and C(max) 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 C(max) after a single dose of sevelamer.


CONCLUSIONS
A single sevelamer dose reduces the C(max) and the AUC of MPA. Its intake for several days does not significantly influence CsA kinetics.
Department of Pediatric Nephrology, Charité, Humboldt University, Berlin, Germany. anne-kathrin.pieper@charite.de
Anne-Kathrin
AK
Pieper
Franziska
F
Buhle
Steffen
S
Bauer
Ingrid
I
Mai
Klemens
K
Budde
Dieter
D
Haffner
Hans-Hellmut
HH
Neumayer
Uwe
U
Querfeld
D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004852:Epoxy Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D010710:Phosphates / Q000378:metabolism; D011073:Polyamines; D011095:Polyethylenes / Q000009:adverse effects* / Q000627:therapeutic use; D000069603:Sevelamer
D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010710:Phosphates; D011073:Polyamines; D011095:Polyethylenes; D016572:Cyclosporine; D000069603:Sevelamer; D009173:Mycophenolic Acid