CYP2C9 Activity Evaluated With a Simple Finger Prick
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    


Intervention name(s): flurbiprofen; flurbiprofen, rifampicin; flurbiprofen + fluconazole
Intervention type(s): Drug; Drug; Drug
Intervention description(s): assessment of flurbiprofen plasmatic and capillary rates; assessment of flurbiprofen plasmatic and capillary rates; assessment of flurbiprofen plasmatic and capillary rates
Intervention MeSH terms: Rifampin; Fluconazole; Flurbiprofen
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic