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.
Pieper
Anne-Kathrin
AK
Department of Pediatric Nephrology, Charité, Humboldt University, Berlin, Germany. anne-kathrin.pieper@charite.de
Buhle
Franziska
F
Bauer
Steffen
S
Mai
Ingrid
I
Budde
Klemens
K
Haffner
Dieter
D
Neumayer
Hans-Hellmut
HH
Querfeld
Uwe
U
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