CYP3A4 Activity in Patients With Prostate Cancer Versus Male Patients With Other Solid Tumours
Status:
Recruiting
Trial end date:
2023-08-01
Target enrollment:
Participant gender:
Summary
The hepatic enzyme, cytochrome P450 3A4 (CYP3A4) is important for the metabolism of many
drugs including taxanes. Previous reported studies reported a decreases in docetaxel exposure
in prostate cancer patients compared to patients with other solid tumours. The difference was
1.8-fold for intravenous administration and 2.8-fold for oral administration.
The underlying mechanism for these observations remains to be elucidated. The lower docetaxel
exposure with IV and oral docetaxel treatment might be related to a higher CYP3A4 activity in
prostate cancer patients. Therefore, it is important to directly compare the CYP3A4 activity
with a phenotyping test in prostate cancer patients and patients with other types of solid
tumours.
This is an in vivo phenotyping studying using midazolam as a probe for CYP3A4 activity in
patients with prostate cancer and patients with other solid tumours. The primary objective is
the comparison of CYP3A4 activity in prostate cancer patients versus male patients with other
types of solid tumours by use of an oral midazolam phenotyping test. Secondary objectives
are: (1) measurement of plasma concentrations of midazolam and it's two primary metabolites
(1'-hydroxy midazolam and 4'-hydroxy midazolam), (2) determination of the metabolite
pharmacokinetics of midazolam. (3) retrospective assessment of single nucleotide
polymorphisms of CYP3A4. The exploratory objective is to differentiate between
gastro-intestinal and hepatic CYP3A4 activity with oral and intravenous administration of
midazolam.