CYP2C9 Activity Evaluated With a Simple Finger Prick
Information source: University Hospital, Geneva
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy Volunteers
Intervention: flurbiprofen (Drug); flurbiprofen, rifampicin (Drug); flurbiprofen + fluconazole (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: University Hospital, Geneva
Summary
The cytochrome P450 enzymes (CYP) are the major drug-metabolizing enzyme system in humans. A
great inter- individual variability affects the activity of these enzymes, and consequently
the plasma drug concentrations resulting in different pharmacodynamic effects and occurrence
of effect sides. Environmental factors, diet, drugs or genetics are responsible for this
variability. Genetic factors are very important since the majority of these enzymes are
highly polymorphic. For example, over 80 CYP2D6 allelic variants have been discovered so far
and are associated to the absence, a decrease, or an increase in enzyme activity. Most
polymorphisms were detected by adverse reactions occurring in a group within the population
after normal doses of drugs had been administrated. Those patients experiencing adverse
reactions often had a reduced capability to metabolize certain drugs. In clinical therapy,
this variability has important consequences including the lack of response to a treatment
and/or adverse drug reactions. In order to reduce these potentially unwanted events possibly
leading to sever adverse reactions or death, it might therefore be of decisive interest to
be able to assess the activity of these enzymes at the individual level. Two approaches may
be used to assess CYPs activities, genotype and phenotype. Genotype is based on DNA analysis
and polymorphism detection. Phenotype consists of administration of "model" drug or probe
drug metabolized by a specific CYP and a determination of a ratio between the drug and its
metabolite in plasma or urine. The principal drawback of the phenotyping methods is the
urine collection overnight or at least 8 hours after the administration of probe test. This
procedure is very tedious and time consuming for the patient as well as for the medical
staff. The test can be performed in plasma or blood 1-2 hours after probe administration.
However, this procedure is invasive and needs an important volume of blood (6 ml). Recently,
a novel approach has been developed for the quantitative determination of circulating drug
concentrations using dried blood spots (DBS) on filter paper obtained with a simple finger
prick. Due to the small blood volume required (about 10 µL) compared to conventional
sampling, this minimally invasive method provides a patient-friendly alternative for blood
collection in patient population where venous sampling is unethical or impossible
(pediatrics).
In addition, DBS sampling does not require the use of anticoagulant, plasma separation and
decreases contact with infectious material. Furthermore, dried blood spots can be easily
stored and shipped to analytical laboratories without using refrigerated devices.
Thanks to the new developments in analytical techniques (mass spectrometry), which permit
quantitative analysis from very small volume of blood. DBS sampling represents a powerful
tool for the biomedical analyses, particularly in pharmacokinetic studies where several
blood samples are needed and for phenotyping procedures.
Clinical Details
Official title: Evaluation of the CYP2C9 Activity With Dried Blood Spots on Filter Paper Obtained With a Simple Finger Prick
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Primary outcome: Flurbiprofen plasma and capillary rates in presence/absence of CYP2C9 inhibitor or inducer
Secondary outcome: Correlation between CYP2C9 Genotype and Phenotype
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Male.
Criteria:
Exclusion Criteria:
- Allergic to the administrated drugs
- Contact lense
- History of peptic ulcer or digestive bleeding
- Long QT
- Impaired hepatic tests (ASAT, ALAT, GGT, BILI)
- Taking drugs interacting with CYP2C9 activity
- Concomitant disease interacting with CYP2C9 activity
Locations and Contacts
University Hospitals, Geneva 14 1211, Switzerland
Additional Information
Starting date: November 2009
Last updated: January 10, 2011
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