C2 and C0 values for monitoring cyclosporine therapy in stable heart transplant recipients.
BACKGROUND
We sought to evaluate the behavior of C2 values and their correlation with acute rejection episodes and cyclosporine (CyA) side effects in heart transplant patients whose immunosuppressive therapy, was monitored with C0 trough levels.


METHODS
Sixty stable patients who had received heart transplants from 3 months to 60 months prior were randomly observed from September 2001 to June 2004. Four area under the concentration-time curves (AUC) were performed on each patient, a total of 240 AUC curves.


RESULTS
Regarding the variability of CyA absorption, two groups of patients were distinguished: group A, "constant absorbers," namely, low variability (<15%) of CyA absorption; group B, "inconstant absorbers" patients with higher (>15%) variability of absorption. Group B patients showed more acute rejection episodes (41%) than group A (19%). CyA side effects were more serious in patients with higher variability of absorption: systemic hypertension, neurological disorders, hyperlipidemia, and gum hyperplasia; Group B patients who developed CyA side effects showed higher maximum and mean C2 levels (P < .05) than group A patients. No differences were found with regard to renal dysfunction between the two groups: all patients showed a mean increase of serum creatinine by at least 50% compared to the baseline value.


CONCLUSIONS
Higher C2 levels were not sufficient to predict acute rejection compared to lower but constants, C2 levels. Patients with inconstant absorption were more often overexposed to CyA than underexposed, developing more side effects than patients with lower variability of absorption. Monitoring CyA therapy with C0 and C2 may prevent over- or underexposure to the drug.
Diciolla
F
F
Department of Cardiothoracic Surgery, University of Siena, Siena, Italy. Diciolla@aliceposta.it
Scolletta
S
S
Berti
L
L
Maccherini
M
M
Federici
D
D
Bernazzali
S
S
Lisi
G
G
Chiavarelli
M
M
D000284:Administration, Oral; D019540:Area Under Curve; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D007166:Immunosuppressive Agents; D016572:Cyclosporine