title: Tacrolimus dosing requirements and concentrations in adult living donor liver transplant recipients.
abstract: Living donor liver transplantation in adult recipients is becoming increasingly common. The liver metabolizes most drugs, including immunosuppressive agents. Right-lobe grafts used in adult living donor liver transplantation consist of only 50% to 60% of the total liver. The purpose of this study is to determine whether there is a difference between tacrolimus doses and concentrations in patients who received a partial liver transplant from a living donor (LRD) versus those who received a whole-liver transplant from a cadaveric donor (CAD). Thirteen LRD recipients and 13 CAD recipients who underwent transplantation between April 1998 and July 2000 were included in this analysis. A CAD control group matched for age, sex, and race was used for comparison. Tacrolimus doses and concentrations were analyzed weekly for the first 4 weeks, then monthly for 6 months posttransplantation. There was no difference in acute rejection rates, renal and liver function test results, or number of potentially interacting medications administered between groups. LRD recipients required significantly lower doses of tacrolimus compared with CAD recipients at 2 weeks (0.058 v 0.110 mg/kg/d; P <.01), 3 weeks (0.068 v 0.123 mg/kg/d; P <.02), 4 weeks (0.086 v 0.141 mg/kg/d; P <.02), 2 months (0.097 v 0.141 mg/kg/d; P <.03), and 3 months (0.099 v 0.138 mg/kg/d; P <.03). Tacrolimus 12-hour trough concentrations were similar between groups at all times except for 2 weeks posttransplantation, when LRD recipients' concentrations were significantly greater than those of CAD recipients (12.4 v 9.5 ng/mL; P <.03). In addition, in the first month posttransplantation, LRD recipients were more likely to have greater concentrations of tacrolimus (>15 ng/mL; 22.1% v 9.2%; P <.01). In conclusion, LRD recipients have significantly decreased tacrolimus dosing requirements compared with CAD recipients during the first 3 months posttransplantation despite having similar tacrolimus concentrations.
authors.affiliation: Department of Pharmacy, University of North Carolina School of Pharmacy and Medicine, Chapel Hill, NC 27599, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Taber
authors.forename: Robert E
authors.initials: RE
authors.lastname: Dupuis
authors.forename: Amy L
authors.initials: AL
authors.lastname: Fann
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Andreoni
authors.forename: David A
authors.initials: DA
authors.lastname: Gerber
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Fair
authors.forename: Mark W
authors.initials: MW
authors.lastname: Johnson
authors.forename: Roshan
authors.initials: R
authors.lastname: Shrestha
mesh_terms: D000328:Adult; D002102:Cadaver; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D016031:Liver Transplantation / Q000379:methods; D019520:Living Donors; D009994:Osmolar Concentration; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus