Target range maximum of cyclosporine blood concentration two hours post dose in stable liver transplant patients

Recently, single blood level measurement 2 hours after cyclosporine administration (C2) is taken as a more sensitive indicator of drug exposure in de novo transplant recipients than trough levels (C0). However, few studies focused on the determination of the C2 target range maximum and its associated adverse events in stable liver recipients. This prospective study was designed to assess the relative risk of developing CsA related side effects in patients with high C2-levels. Adverse effects were determined clinically, and by using a specially designed questionnaire. Eventual adverse events as well as C2 levels were determined repeatedly up to 4 times in 3-months intervals (observation period 9 +/- 3 months) in 36 long-term liver recipients (1-13.5 years post-transplant), in addition to conventional C0 levels. Cyclosporine dose was adjusted according to a predefined C0 target level range and clinical status. Totally 103 questionnaires and the corresponding paired CsA blood level records were obtained. C0 levels and C2 levels ranged from 90 to 287 (143 +/- 31) ng/ml and from 212 to 1358 (672 +/- 203) ng/ml respectively. No patient experienced a rejection episode during the observation period, demonstrating the efficiency of the immunosuppressive therapy. However, 33/36 patients (91%) showed symptoms attributable to CsA therapy. C2 levels above 750 ng/ml, determined at least twice in an interval of 3 months, were identified as a relevant risk factor for the presence of multiple adverse effects, which were defined as the combination of hypertension, renal insufficiency and more than two neurological complaints (RR = 3.11, p<0.01). This risk population was not completely identified by determination of C0 level.