Switching monitoring of emulsified cyclosporine from trough level to 2‐hour level in stable liver transplant patients

After orthotopic liver transplantation (OLT) many patients use emulsified cyclosporine. Recent data showed that blood levels 2 hours after dosing (C‐2) better reflect systemic exposure to the drug (area under the blood concentration time curve) than trough levels (C‐0) do. We investigated difference in dosage, creatinine clearance (CrCl), blood pressure (BP), freedom from rejection, and relation of C‐2, C‐0, and AUC while switching 31 stable patients more than 6 months after OLT from C‐0 to C‐2 monitoring. With C‐0 between 90 and 150 ng/mL we collected 24‐hour urine, while blood samples were taken at t = 0, 1, 2, 3, 4, 6, and 8 hours after dosing to measure cyclosporine, creatinine, liver tests, and blood pressure and calculated AUC and CrCl. Target AUC was calculated based on C‐0. Then the dose was adjusted to two subsequent C‐2 values of 600 ng/mL ± 15%, the above was repeated, and the differences were assessed. Cyclosporine dose was reduced in 21/31 patients (68%) and remained unchanged in 10/31 patients (32%) after conversion. Mean lowering was 69 mg daily (26.9 %, P < 0.0001). After dose reduction the mean increase of CrCl was 7.93 ml/min (11.6%, P = 0.016). Only systolic and mean morning BP decreased slightly but significantly. C‐2 correlated better with AUC 0–12 (r2 = 0.75) than C‐0 (r2 = 0.64). However, 13/21 patients had a second AUC below target AUC and 2 of these 13 patients developed rejection after conversion to C‐2 levels. In conclusion, while C‐0 monitoring frequently results in overdosing and more renal dysfunction, C‐2 monitoring may lead to episodes of underdosing and rejection. Therefore better ways of monitoring cyclosporine dosing need to be devised. (Liver Transpl 2004;10:183–189.)