Pharmacokinetics of tacrolimus in living donor liver transplant and deceased donor liver transplant recipients

Ashok Jain, Raman Venkataramanan, Rajeev Sharma, Tai Kwong, Mark Orloff, Peter Abt, Randeep Kashyap, Georgious Tsoulfas, Pam Batzold, Mary Williamson, Adel Bozorgzadeh

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10 Scopus citations

Abstract

Introduction. 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. Patients and 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) forDDLT(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. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)554-560
Number of pages7
JournalTransplantation
Volume85
Issue number4
DOIs
StatePublished - Dec 1 2008

All Science Journal Classification (ASJC) codes

  • Transplantation

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    Jain, A., Venkataramanan, R., Sharma, R., Kwong, T., Orloff, M., Abt, P., Kashyap, R., Tsoulfas, G., Batzold, P., Williamson, M., & Bozorgzadeh, A. (2008). Pharmacokinetics of tacrolimus in living donor liver transplant and deceased donor liver transplant recipients. Transplantation, 85(4), 554-560. https://doi.org/10.1097/TP.0b013e3181642c95