Effects of CKD and haemodialysis on hepatic drug metabolism
Research type
Research Study
Full title
Investigation of the effects of chronic kidney disease and haemodialysis on hepatic drug metabolism
IRAS ID
146477
Contact name
Iain MacPhee
Contact email
Sponsor organisation
St George's University Of London
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Patients with chronic kidney disease (CKD) often take multiple medications. However, our understanding of drug metabolism in patients with CKD is incomplete. There are some published data indicating that the liver does not metabolise drugs normally in patients with CKD although this remains unclear. This study aims to investigate the effect of chronic kidney disease (CKD) on the clearance of medications which are metabolised by liver CYP3A enzymes.
Subjects will be patients on chronic haemodialysis, and patients with functioning kidney transplants (controls). Patients will be given one of these medications, midazolam, at a very low dose. We know from previous published work that this ia a safe and effective method of measuring CYP3A enzyme activity. Concentrations of midazolam in their blood will be checked after 4 hours, to establish how much of the drug has been broken down. Other blood tests will also be checked to try to identify a cause for any effect observed, and a sample will be saved for future laboratory experiments.
Controls will be studied once. In dialysis patients the experiment will be completed twice – once immediately before a regular dialysis session on a Monday or Tuesday when they will have gone for 3 days without dialysis (to maximise the degree of uraemia at the time of the study), and once immediately after a different dialysis session.
All other aspects of the patient’s clinical care will continue unaltered during the study period.
REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
15/NW/0773
Date of REC Opinion
3 Nov 2015
REC opinion
Further Information Favourable Opinion