Pharmacokinetics of a once-daily tacrolimus formulation in first nations and caucasian liver transplant recipients

Patient ethnicity may influence the pharmacokinetics (PK) of tacrolimus. Because the Canadian First Nations (FN) constitute a large and increasing segment of the liver transplant population, we undertook to determine whether PK differences exist for a once-daily, extended release formulation of tacrolimus (Advagraf) in FN compared to Caucasian (CAUC) liver transplant recipients. Following achievement of a steady state with Advagraf, blood samples were drawn at 0, 1, 2, 4, 6, 8 and 24 hours for whole blood tacrolimus levels by commercial immunoassay and CYP3A4 and CYP3A5 allele analyses were performed by polymerase chain reactions. Nineteen subjects participated in the study (7 FN and 12 CAUC). The FN cohort had significantly higher AUC (214 +/- 48 versus 168 +/- 25, P < 0.05), Cmax (16.7 +/- 4.4 ng/ml versus 11.3 +/- 1.7 ng/ml, P < 0.05), Cmin (6.1 +/- 1.0 ng/ml versus 4.7 +/- 0.5 ng/ml, P < 0.05) and shorter Tmax (1.6 +/- 0.2 hours versus 2.8 +/- 0.3 hours, P < 0.05) values than CAUCs. CYP3A4 genotypes were C/C in both cohorts, while the CYP3A5 *1/*3 allele was present in 2/5 FN and 0/9 CAUC. The results of this study indicate that once-daily, extended release Advagraf results in higher blood tacrolimus levels and shorter times to Cmax in FN compared to CAUC liver transplant recipients.