Transplant international : official journal of the European Society for Organ Transplantation | 2021
Pharmacokinetics of a Once Daily Tacrolimus Formulation in First Nations and Caucasian Liver Transplant Recipients.
Abstract
BACKGROUND\nPatient ethnicity may influence the pharmacokinetics (PK) of tacrolimus. The Canadian First Nations (FN) constitute a large and increasing segment of the liver transplant population.\n\n\nOBJECTIVE\nTo determine whether PK differences exist for a once daily, extended-release formulation of tacrolimus in FN compared to Caucasian (Cauc) liver transplant recipients.\n\n\nMETHODS\nFollowing a 1:1 mg conversion from immediate- to extended-release tacrolimus and achievement of a steady state on the latter formulation, blood samples were drawn at 0, 1, 2, 4, 6, 8 and 24 hours for whole blood tacrolimus levels by commercial immunoassay. CYP3A4 and CYP3A5 allele analyses were performed by polymerase chain reactions.\n\n\nRESULTS\nNineteen subjects participated in the study (7 FN and 12 Cauc). Unlike Cauc patients, post-conversion Cmin levels did not decrease and were less variable in FN patients. FN patients also had significant shorter Tmax times (1.6±0.2 hours versus 2.8±0.3 hours, p<0.05). Oral clearance, Vd, AUCs, Cmax and Cmin levels were similar in the two cohorts. CYP3A4 genotypes were C/C in both cohorts while the CYP3A5 *1/*3 allele, was present in 2/5 FN and 0/9 Cauc.\n\n\nCONCLUSIONS\nConversion from immediate- to extended-release tacrolimus results in no significant decrease in Cmin levels, less variable Cmin levels and a shorter time to Tmax in FN compared to Cauc liver transplant recipients.