Pharmacokinetics of Tacrolimus Immediately after Liver Transplantation

Measurements of tacrolimus concentration after organ transplantation are accepted methods to guide adjustments in drug doses. The aim of this study was to determine tacrolimus pharmacokinetic variability early after liver transplantation. Pharmacokinetic profiles were obtained at days one or two after surgery. Blood samples obtained at 0, 1, 2, 3, 4, 5, 7, 9 and 10 h after oral dosing and were analyzed using a microparticle enzyme-immunoassay. The results of median dose-equalised tacrolimus concentrations during one dosage interval demonstrated a 10to >100-fold range of values in pharmacokinetic variables exemplified by a 31-fold range of AUC (mean, 40.1 μg.h/L; range, 4.2-124 μg.h/L). There was a delayed absorption peak (mean; 2.2 h, range; 0.1-13 h), continued drug accumulation and an overall approximation to a single compartment model. Examination of the frequency distributions within the entire population of liver recipients indicated a bimodality which further analysis related to aetiology of disease. We conclude that an acute or chronic indication for transplantation appears to be a major determinant of inter-individual variability in pharmacokinetic parameters and leads to differences consistent with the bimodal distributions in AUC (p = 0.004), Cmax (p = 0. 003) and Cmin (p = 0.007).