Steimer et al correlated CYP2D6 and CYP2C19 phenotypes with adverse side effects during amitriptyline therapy. This can help identify patients who can or should not receive amitriptyline therapy. The authors are from the Technische Universitat Munchen and Bezirkskrankenhaus Haar in Germany.
Parameters:
(1) CYP2C19 phenotype: demethylates amitriptyline to nortriptyline
(2) CYP2D6 phenotype: hydroxylates nortriptyline to 10-OH-nortriptyline (inactive)
CYP2C19 Phenotype
|
Functional Alleles |
Dysfunctional Alleles |
Metabolizer |
|
0 |
2 |
poor |
|
1 |
1 |
intermediate |
|
2 |
0 |
extensive |
|
Alleles |
Phenotype |
|
1 or 2 dysfunctional |
2C19-1 |
|
2 functional |
2C19-2 |
CYP2D6 Phenotype
|
Functional Alleles |
Reduced Function Alleles |
Dysfunctional Alleles |
Metabolizer |
|
2 |
0 |
0 |
ultrarapid |
|
1 |
1 |
0 |
extensive |
|
1 |
0 |
1 |
extensive |
|
0 |
1 |
1 |
intermediate |
|
0 |
0 |
2 |
poor |
where:
• Fully functional alleles are *1 and *2.
• Reduced function alleles are *9, *10 and *41.
• Dysfunctional alleles are *3 to *8.
|
Alleles |
Phenotype |
|
1 or 2 dysfunctional |
2D6-1 |
|
2 functional or reduced function alleles |
2D6-2 |
Phenotype vs Adverse Side Effects
Slow production of nortriptyline and rapid conversion to inactive 10-hydroxy-nortriptyline is associated with no adverse side effects.
Rapid production of nortriptyline and slow conversion to inactive 10-hydroxy-nortriptyline is associated with a high rate of adverse side effects.
|
CYP2C19 |
CYP2D6 |
Risk Group |
Percent Adverse Effects |
|
2C19-1 |
2D6-2 |
low |
0% |
|
2C19-2 |
2D6-2 |
medium low |
16% |
|
2C19-1 |
2D6-1 |
medium high |
67% |
|
2C19-2 |
2D6-1 |
high |
82% |
from Figure 1, page 380
Specialty: Toxicology, Emergency Medicine, Critical Care, Genetics
ICD-10: ,
