Clinical benefit of neoral dose monitoring with cyclosporine 2-HR post-dose levels compared with trough levels in stable heart transplant patients

Background. Based on the excellent correlation between cyclosporine A 2-hr postdose blood levels (C-2) and the area under the concentration versus time curve, are evaluated the clinical benefit of Neoral dose monitoring with C-2 compared trough levels (C-0) in stable heart transplant patients. Methods. We studied 114 stable adult patients followed at the heart transplant clinic, who mere >1 year after surgery. In May 1996 (period 1, follow-up 10+/-4 months), Neoral dose monitoring was based on C-2 (300-600 ng/ml); while in May 1997 (period 2, follow-up 10+/-2 months), it was based on C-0 (100-200 ng/ml). Cyclosporine A levels were measured by an enzyme multiplied immunologic technique. Clinical benefit was defined by the absence of acute rejection, no mortality, no fall in left ventricular ejection fraction >10%, and no increase in serum creatinine >10% (compared with baseline). Results. During period 1, Neoral dose, cyclosporine A, C-0 and C-2, and serum creatinine, decreased by 26, 56, 45, and 2.3%, respectively. At the end of period 2, the same variables increased by 24, 56, 38, and 10%, respectively (P<0.0001). The incidence of acute rejection was similar (period 1: 0.87%, period 2: 0.96%). The left ventricular ejection fraction (initial/final) remained stable (period 1: 57+/-9%/58+/-13%, period 2: 59+/-11%/58+/-10%). Mortality did not differ (period 1: 7.9%, period 2: 9.6%). A clinical benefit was observed in 69.3% of the patients during period 1 vs. 43.3% of the patients during period 2 (P<0.00001). Conclusions. In stable heart transplant patients, a greater clinical benefit was observed when Neoral dose monitoring was performed according to C-2, compared with C-0.