Comparative FK506 Drug Levels of Once Daily Advagraf in First Nations and Caucasian Patients With Liver Transplants
Status:
Completed
Trial end date:
2019-11-27
Target enrollment:
Participant gender:
Summary
Background:
Previous studies have documented differences in the pharmacokinetics (PK) of a once daily
FK506 formulation (Advagraf) based on patient ethnicity. These findings may be of particular
relevance to the First Nations population who constitute a large and increasing segment of
the liver transplant population in Canada.
Aim:
The purpose of the present study is to determine whether PK differences exist for Advagraf in
First Nations compared to Caucasian liver transplant patients.
Objectives:
1. Document and compare PK determinations for Advagraf in First Nations and Caucasian
patients with stable liver transplants.
2. Document and compare CYP3A gene expression profiles in the two ethnic populations.
Study Design:
- single-centre, open-label
- consecutive enrollment (N=8/group)
- self-identified adult First Nations and Caucasian ethnic cohorts
- 7 day steady state conversion (mg/mg/day) from twice to once daily FK506 formulation
- timed blood samples at 0, 1.5, 2, 4, 6, and 24 hours post medication
- PK determinations:concentration at zero time (C0), time to maximum concentration
(Tmax),Area Under the Curve (AUC 0-24), apparent oral clearance (CLoral) and maximum
concentration (Cmax)
Methods:
- whole blood FK506 levels will be measured by UPLC tandem mass spectroscopy
- CYP3A allele analyses will be performed by Dr. Richard Kim, University of Western
Ontario
Relevance:
The results of this study will serve to determine whether present guidelines for conversion
of twice to once daily FK506 formulations need be modified for First Nations liver transplant
patients.