Purpose: Cyclosporine dosing is traditionally based on cyclosporine trough level (C0). Recently, however, it was reported that 2-hour post dose sampling point (C2) represents more precisely area under the curve (AUC) which measures drug
exposure
and that it has better correlations with acute rejection and cyclosporine nephrotoxicity than CO. we evaluated the clinical usefulness of C2 monitoring in living-donor renal transplant recipients during early post-transplant period.
Methods: Thirty-four renal transplant recipients with living related donor were included. Patients are divided into two groups (C0 and C2 group), in an alternating order. They received cyclosporine-based triple immunosuppression
(Cyclosporine,
Prednisolone, Mycophenolate mofetil). In both groups, cyclosporine dosing was based on C0 and C2, respectively, and adjusted to target level (C2: 1,600∼2,000 ng/㎖) Cyclosporine whole blood level was measured by radioimmunoassay. C0, C2 and
AUC0-4
were
measured regularly during early post-transplant period.
Results: For total 34 recipients (C0 group: 16 patients, C2 group: 18 patients), AUC0-4 was measured 95 times. Only 21% of the measurements, 20 of 95, were in the target level, 4,400∼5,500 ng/㎖, while 69% of them, 66 of 95, were less
than
4,400
ng/㎖. In C2 group, 69% of the total measurements for C2, 111 of 162, were less than 1,600 ng/㎖. C2 correlated much more closely with AUC0-4 (R=0.936) than CO (R=0.450). No patient have acute rejection. 41.2% of the total patients, 14 of 34,
haved
cyclosporine hepatotoxicity and 14.7% of them, 5 of 34, haved cyclosporine nephrotoxicity. 31.3% of the patients in CO group, 5 of 16, haved cyclosporine hepatotoxicity and 18.8% of them, 3 of 16, have cyclosporine nephrotoxicity. C2 group haved
cyclosporine hepatotoxicity in a half cases (9 of 18, 50%) and 18.8% of them, 2 of 18, have cyclosporine nephrotoxicity. Between two groups, there was no statistical difference in the correlations with cyclosporine hepatotoxicity and cyclosporine
hepatotoxicity.
Conclusion: C2 is more accurate single-sample marker for AUC0-4 than C0. Considering high frequency of cyclosporine hepatotoxicity and cyclosporine nephrotixicity, the target levels of AUC0 and C2 in living-donor transplantation would be
lowered.
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