Measurement of Intracellular Tacrolimus: Validation Study
Research type
Research Study
Full title
Measurement of Intracellular Tacrolimus: Validation Study
IRAS ID
158442
Contact name
Jennifer Joslin
Contact email
Sponsor organisation
St George’s University of London
Duration of Study in the UK
0 years, 6 months, 30 days
Research summary
Tacrolimus is the most widely-used immunosuppressant drug in new renal transplant recipients in the United Kingdom. There is substantial variation between individuals in the blood drug concentration achieved by a given dose.
The concentration of tacrolimus in whole blood is routinely measured after transplantation as a guide to dose adjustment (therapeutic drug monitoring). Patients can however experience rejection or toxicity despite this value being in the target range. The tacrolimus immunosuppressant effect is mediated through blocking the activity of T-lymphocytes. Direct measurement of the amount of drug in these target cells may be better than our current standard approach with measurement in whole blood.
This study will be divided into two parts: the first step will involve the validation of tacrolimus quantification tests in our laboratory using blood samples from healthy volunteers as the technique for tacrolimus quantification has not yet been validated in our laboratory.
After the completion of the validation study, we will use the described method to validate a method for the determination of tacrolimus in peripheral blood mononuclear cells (PBMCs - a lymphocyte-rich compartment within whole blood).This will involve the correlation of intracellular tacrolimus concentrations in renal transplant recipients, with graft rejection as an indicator of the potential benefit of measurement of intracellular tacrolimus in therapeutic drug monitoring.
We will then determine whether intracellular drug concentrations predict patients who develop acute rejection. We will also study factors including genetics that may influence the amount of tacrolimus inside cells.
This current project is the validation study only.
REC name
London - Chelsea Research Ethics Committee
REC reference
15/LO/0012
Date of REC Opinion
26 Jan 2015
REC opinion
Favourable Opinion