title: The calcineurin activity profiles of cyclosporin and tacrolimus are different in stable renal transplant patients.
abstract: Cyclosporin and tacrolimus remain the cornerstone immunosuppressive drugs in organ transplantation. Dosing and monitoring these drugs is based on pharmacokinetic protocols, but measuring a pharmacodynamic parameter, calcineurin phosphatase (CaN) activity, could be a valuable supplement in determining optimal doses. Forty stable renal transplant patients were investigated three times in a 6-month period. Blood samples were drawn at 0, 1, 2, 3 and 4 h after oral intake of tacrolimus (FK) or cyclosporin at days 1 and 180. At day 90, one blood sample at trough level (FK) or C2 level (cyclosporin A, CsA) was drawn. CaN activity was determined in whole blood as the release of 32P from a phosphorylated peptide. Activity of the 32P was quantitated by liquid scintillation and results converted to Units CaN, utilizing a calibration curve with CaN. We demonstrated that calcineurin activity profiles at days 1 and 180 were the same for both drugs. Furthermore, we found that patients treated with tacrolimus or cyclosporin displayed different calcineurin activity profiles. We found that cyclosporin displayed greater calcineurin inhibition than tacrolimus. We have demonstrated that the two drugs exert significantly different effects on calcineurin activity in renal transplant patients with stable, well-functioning grafts and that tacrolimus-treated patients can maintain good, stable graft function with minimal CaN inhibition.
authors.affiliation: Department of Renal Medicine C, Research Laboratory C, Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardsvej, Aarhus N, Denmark.
authors.forename: Pernille B
authors.initials: PB
authors.lastname: Koefoed-Nielsen
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Karamperis
authors.forename: Carsten
authors.initials: C
authors.lastname: Højskov
authors.forename: Jørgen Hjelm
authors.initials: JH
authors.lastname: Poulsen
authors.forename: Kaj Anker
authors.initials: KA
authors.lastname: Jørgensen
mesh_terms: D000328:Adult; D000368:Aged; D019703:Calcineurin / Q000378:metabolism*; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011446:Prospective Studies; D016559:Tacrolimus / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D016572:Cyclosporine; C120817:calcineurin phosphatase; D019703:Calcineurin; D010744:Phosphoric Monoester Hydrolases; D016559:Tacrolimus