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 (C2) and the area under the concentration versus time curve, we evaluated the clinical benefit of Neoral dose monitoring with C2 compared trough levels (C0) in stable heart transplant patients.


METHODS
We studied 114 stable adult patients followed at the heart transplant clinic, who were >1 year after surgery. In May 1996 (period 1, follow-up 10+/-4 months), Neoral dose monitoring was based on C2 (300-600 ng/ml); while in May 1997 (period 2, follow-up 10+/-2 months), it was based on C0 (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, C0 and C2, 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+/-91%/58+/-13%, period 2: 59+/-11d/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 C2, compared with C0.
Cantarovich
M
M
Department of Medicine, Royal Victoria Hospital, McGill University Health Center, Montréal, Québec, Canada.
Elstein
E
E
de Varennes
B
B
Barkun
J S
JS
D000208:Acute Disease; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000401:mortality; D013318:Stroke Volume; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D016572:Cyclosporine