title: Living donor liver transplant recipients achieve relatively higher immunosuppressant blood levels than cadaveric recipients.
abstract: Two recent brief reports suggest that recipients of living donor liver transplants achieve higher levels of immunosuppressive agents than cadaveric (CAD) liver transplant recipients administered the same dose. These results could have important implications regarding the dosing of immunosuppressives in living donor liver transplant recipients. We report our findings relative to immunosuppressive doses and levels in a cohort of 46 living donor liver transplant recipients. Immunosuppressive blood levels and doses were recorded weeks 1, 2, 3, and 4 and months 2, 3, 4, 5, and 6 for 46 living donor liver transplant recipients and 66 matched CAD liver transplant recipients who underwent transplantation between August 1997 and May 2001. The ratio of level to dose also was recorded at each interval. The mean overall cyclosporine A dose was similar in living donor liver transplant recipients (323 mg/d) compared with CAD recipients (344 mg/d; P = not significant [NS]). The mean overall tacrolimus dose was 15% lower in patients who underwent living donor liver transplantation (LDLT; 5.7 mg/d) than CAD transplantation (6.7 mg/d), although statistical significance was not achieved (P =.08). The mean overall cyclosporine A level was 18% higher in those undergoing LDLT (275 ng/mL) than CAD transplantation (234 ng/mL; P =.015). The mean overall tacrolimus level was the same in living donor liver transplant recipients (10.8 ng/mL) and CAD recipients (10.2 ng/mL; P = NS). The overall cyclosporine A level-dose ratio was 26% higher for those undergoing LDLT (0.83) than CAD transplantation (0.66; P =.01). The overall tacrolimus level-dose ratio was 26% higher for those undergoing LDLT (1.82) than CAD transplantation (1.44; P =.01). In conclusion, (1) living donor liver transplant recipients achieve higher blood levels of tacrolimus and cyclosporine A for a given dose compared with CAD recipients, and (2) this difference is observed up to 6 months after transplantation, when hepatic regeneration is completed.
authors.affiliation: Division of Gastroenterology/Hepatology, University of Colorado Health Sciences Center, Denver, CO, USA. james.trotter@uchsc.edu
authors.forename: James F
authors.initials: JF
authors.lastname: Trotter
authors.forename: Nancy
authors.initials: N
authors.lastname: Stolpman
authors.forename: Michael
authors.initials: M
authors.lastname: Wachs
authors.forename: Thomas
authors.initials: T
authors.lastname: Bak
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kugelmas
authors.forename: Igal
authors.initials: I
authors.lastname: Kam
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002102:Cadaver; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D016559:Tacrolimus