Download Slide 1

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts
no text concepts found
Transcript
Implementation of CYP2C19
Genotyping for Clopidogrel
Gwen McMillin, PhD, DABCC (CC,TC)
July 27, 2010
Outline
• Demand for CYP2C19 genotyping
• Laboratory considerations
• Reporting considerations
• Other uses for CYP2C19 genotyping
CYP2C19 Orders July 2009 – June 2010
~40-fold increase in Q4 vs Q1 test volumes
CYP2C19 Patients (Q4)
• Average age: 70 yrs
(median 72 yrs)
• 55% male
• 37 states
Distribution of alleles detected (Q4)
Negative
*2
*3
Predicts PM
*4
*6
*8
*17
Predicts UM
Laboratory Considerations
• Specimen: blood, saliva, buccal swab
• Guidelines and standards: CAP, NYDOH, ACMG
• Quality control: no template, and previously
characterized samples or commercial sources
• Proficiency testing: CAP Pharmacogenetics
Report Content
• Collection, specimen, and patient details
• Results (genotype), evidence of review
• Analytical
–
–
–
–
Method
List of all variants detected, using standard nomenclature
Limitations of testing
ASR status (if applicable)
• Clinical
–
–
–
–
Interpretation
Suggestions for additional or alternative testing
References (if applicable)
Access to consultation (genetic counselor, director)
MOL.3600, CAP, Molecular Pathology, 2009
“Laboratory reports should be designed to
convey patient results effectively to a nonexpert physician. This includes documentation
of the analytical procedure used or the
commercial kit version accompanied by an
interpretation of findings”
Possible algorithm for clopidogrel
Two PM variants
Genotype
CYP2C19
Alternate drug
(e.g., prasugrel)
Monitor response
One PM variant
No PM
Variants
or CYP2C19*17 only
Active drug expected
Drug-drug interactions?
Monitor response
Consider alternate drug
Consider escalated dose
Monitor response
Turnaround Time?
Clinical need
Laboratory and
cost efficiency
Other uses for CYP2C19 Genotyping
• Drug substrate examples
– Antidepressants: amitriptyline, imipramine,
trimipramine, citalopram, sertraline
– Anxiolytic: diazepam
– Anticonvulsant: phenytoin
– Muscle relaxant: carisoprodol
– Gastrointestinal: omeprazole, lansoprazole
– Infection: voriconazole, nelfinavir, proguanil
– Oncology: tamoxifen, cyclophosphamide
– Cardiology: r-warfarin, propranolol
• Define role of CYP2C19 in metabolism
• Content of CYP2C19 testing
Possible Scenarios for Utility
• CYP2C19 is a major pathway
– Inactivates drug
– Activates drug
Impairment could
interfere with
expected drug
activation or
inactivation
• CYP2C19 is a minor pathway
– Inactivates drug
– Activates drug
CYP2C19*17 could
“accelerate” PK or
convert CYP2C19
from a minor to a
major pathway
• Must consider potential for drug-gene
interactions and drug-drug interactions