Pharmacokinetics of tacrolimus in living donor liver transplant and deceased donor liver transplant recipients.
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.
Jain
Ashok
A
Department of Surgery, Division of Solid Organ Transplant, University of Rochester Medical Center, Rochester, NY, USA. ashok_jain@urmc.rochester.edu
Venkataramanan
Raman
R
Sharma
Rajeev
R
Kwong
Tai
T
Orloff
Mark
M
Abt
Peter
P
Kashyap
Randeep
R
Tsoulfas
Georgious
G
Batzold
Pam
P
Williamson
Mary
M
Bozorgzadeh
Adel
A
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
D007166:Immunosuppressive Agents; D003404:Creatinine; D016559:Tacrolimus