CYP2C9 Activity Evaluated With a Simple Finger Prick

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01026714
First received: December 1, 2009
Last updated: January 10, 2011
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Healthy Volunteers
Drug: flurbiprofen
Drug: flurbiprofen, rifampicin
Drug: flurbiprofen + fluconazole
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Evaluation of the CYP2C9 Activity With Dried Blood Spots on Filter Paper Obtained With a Simple Finger Prick

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Flurbiprofen plasma and capillary rates in presence/absence of CYP2C9 inhibitor or inducer [ Time Frame: 3 singles days spaced out with one week wash-out periods ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlation between CYP2C9 Genotype and Phenotype [ Time Frame: one day ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: November 2009
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: flurbiprofen 50mg po Drug: flurbiprofen
assessment of flurbiprofen plasmatic and capillary rates
Experimental: flurbiprofen 50 mg po + CYP2C9 inducer Drug: flurbiprofen, rifampicin
assessment of flurbiprofen plasmatic and capillary rates
Experimental: flurbiprofen 50 mg po + CYP2C9 inhibitor Drug: flurbiprofen + fluconazole
assessment of flurbiprofen plasmatic and capillary rates

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01026714

Locations
Switzerland
University Hospitals
Geneva 14, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
  More Information

No publications provided

Responsible Party: Pr Jules Desmeules, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT01026714     History of Changes
Other Study ID Numbers: MICRO CYP2C9
Study First Received: December 1, 2009
Last Updated: January 10, 2011
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Fluconazole
Rifampin
Flurbiprofen
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014