title: Pharmacokinetics of tacrolimus in living donor liver transplant and deceased donor liver transplant recipients.
abstract: BACKGROUND
  Hepatic dysfunction is an important determinant of the clearance of tacrolimus; however, the impact of reduced hepatic mass in living donor liver transplant (LDLT) patients on the drug exposure and clearance of tacrolimus is not known. AIM.: The aim of the present study is to compare the dosage, concentration and pharmacokinetics parameters of tacrolimus between LDLT and deceased donor liver transplant (DDLT) recipients.
  
  
  METHODS
  Daily doses used and trough concentrations measured were compared in 12 LDLT and 12 DDLT patients. Multiple blood samples were taken over one dosing interval after oral tacrolimus administration, and pharmacokinetics differences were compared.
  
  
  RESULTS
  The mean tacrolimus dosage in first 14 postoperative days was (0.06 mg/kg/day) for LDLT and (0.09 mg/kg/day) for DDLT (P=0.0001). Despite the lower doses used, mean trough concentration was significantly greater in LDLT as compared with DDLT (8.8+/-2.5 ng/mL vs. 6.79+/-1.5 ng/mL, respectively, P=0.013). On the day of the pharmacokinetic study, minimum Concentration (Cmin), 12-hr postdose concentration (Clast), and average concentration (Cavg) were significantly greater in LDLT as compared with DDLT (LDLT: 6.6+/-2.4 ng/mL, 7.2+/-1.8 ng/mL, 8.9+/-3.0 ng/mL; DDLT: 4.3+/-1.0 ng/mL, 4.9+/-1.6 ng/mL, 5.9+/-1.4 ng/mL, P=0.02, 0.04, and 0.02, respectively). Dose normalized AUC was 37.7% greater and clearance, 47.5% lower in LDLT as compared with DDLT.
  
  
  CONCLUSIONS
  Although not statistically significant, the dose normalized AUC was 37.7% greater and clearance 47.5% lower in LDLT as compared with DDLT. An initial tacrolimus dose reduction of about 30-40% may be prudent in LDLT compared with DDLT recipients.
authors.affiliation: Department of Surgery, Division of Solid Organ Transplant, University of Rochester Medical Center, Rochester, NY, USA. ashok_jain@urmc.rochester.edu
authors.forename: Ashok
authors.initials: A
authors.lastname: Jain
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
authors.forename: Rajeev
authors.initials: R
authors.lastname: Sharma
authors.forename: Tai
authors.initials: T
authors.lastname: Kwong
authors.forename: Mark
authors.initials: M
authors.lastname: Orloff
authors.forename: Peter
authors.initials: P
authors.lastname: Abt
authors.forename: Randeep
authors.initials: R
authors.lastname: Kashyap
authors.forename: Georgious
authors.initials: G
authors.lastname: Tsoulfas
authors.forename: Pam
authors.initials: P
authors.lastname: Batzold
authors.forename: Mary
authors.initials: M
authors.lastname: Williamson
authors.forename: Adel
authors.initials: A
authors.lastname: Bozorgzadeh
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001806:Blood Urea Nitrogen; D002102:Cadaver; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D008107:Liver Diseases / Q000601:surgery; D016031:Liver Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014019:Tissue Donors
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D016559:Tacrolimus