title: Switching monitoring of emulsified cyclosporine from trough level to 2-hour level in stable liver transplant patients.
abstract: 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 AUC0-12 (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.
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Langers
authors.forename: Serge C L M
authors.initials: SC
authors.lastname: Cremers
authors.forename: Jan
authors.initials: J
authors.lastname: den Hartigh
authors.forename: Roeland A
authors.initials: RA
authors.lastname: Veenendaal
authors.forename: W Rogier
authors.initials: WR
authors.lastname: ten Hove
authors.forename: Jan
authors.initials: J
authors.lastname: Ringers
authors.forename: Cornelis B H W
authors.initials: CB
authors.lastname: Lamers
authors.forename: Bart
authors.initials: B
authors.lastname: van Hoek
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004655:Emulsions; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood*; D007668:Kidney / Q000503:physiopathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D011184:Postoperative Period; D013997:Time Factors
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine