C2 and C0 values for monitoring cyclosporine therapy in stable heart transplant recipients.

Introduction. We sought to evaluate the behavior of C-2 values and their correlation with acute rejection episodes and cyclosporine (CyA) side effects in heart transplant patients whose immunosuppressive therapy, was monitored with C-0 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 13, "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 C-2 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. Conclusion. Higher C-2 levels were not sufficient to predict acute rejection compared to lower but constants, C-2 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 theraphy with C-0 and C-2 may prevent over- or underexposure to the drug.