Problems of cyclosporine absorption profiling using C2-monitoring.
The present study sought to validate the concept of C2 monitoring in 41 de-novo transplant patients treated with microemulsion of cyclosporine, mycophenolatesodium, steroids and basiliximab.


RESULTS
After 6 months patient and graft survival was 98%, rejection rate was 19%. In the first week only a few patients achieved the suggested C2 levels (19% > 1500, 50% > 1200 ng/ml) despite an increased cyclosporine (CsA) dose. After 14 days 63% of patients reached C2 > 1500 ng/ml (83% C2 > 1200) despite decreased CsA dose. 35% of patients had intermittent high C0 (> 300) and low C2 (< 800), suggesting poor and/or slow absorption. Most of them suffered from CsA toxicity. There was a significant (p < 0.05) change of absorption as measured by C2/C0 leading to an increase of C2/dose.


CONCLUSIONS
C2 monitoring may be useful to better estimate the CsA exposure in individual patients; however our results indicate some limitations of the current concept of C2 monitoring. Despite increase of dosage many patients do not reach the proposed levels. A significant proportion of patients are poor and/or slow absorbers. CsA toxicity may not be detected by C2 monitoring alone. With the use of basiliximab and mycophenolatesodium lower target levels seem to be sufficient.
Schuetz
M
M
Department of Nephrology, Charité, Schumannstr. 20 / 21, D-10117 Berlin, Germany. manuela.schuetz@charite.de
Einecke
G
G
Mai
I
I
Neumayer
H-H
HH
Glander
P
P
Waiser
J
J
Fritsche
L
L
Budde
K
K
D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000077552:Basiliximab; D003175:Complement C2 / Q000378:metabolism*; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007390:International Agencies; D007408:Intestinal Absorption / Q000502:physiology*; D007668:Kidney / Q000187:drug effects*; D016030:Kidney Transplantation / Q000276:immunology*; D009173:Mycophenolic Acid / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D013256:Steroids / Q000627:therapeutic use
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D003175:Complement C2; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D013256:Steroids; D016572:Cyclosporine; D000077552:Basiliximab; D009173:Mycophenolic Acid