Textbook of Personalized Medicine - Second Edition [2015]

104

Table 4.2 Examples of mutation of the enzyme CYP450

CYP450
enzyme Prototype substrate Allele Mutation
CYP2D6 Debrisoquine 2XN Genetic duplication
4 Defective splicing
10 Gene deletion and single amino acid
substitution
17 Single amino acid substitution
CYP2C19 S-mephenytoin 2 Aberrant splice site
3 Premature stop codon
CYP2C9 Phenytoin, tolbutamide,
warfarin

2 and 3 Single amino acid substitution leading to
altered substrate specifi city
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Isoform of CYP450

Frequency distribution of

drugs metabolized (%)

CYP3A4 50

CYP2D6 20

CYP2C9 10

CYP2C19 5

CYP1A2, CYP2E1, CYP1A2

and unidentifi ed forms

15

Total 100

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Table 4.3 Frequency
distribution of drugs
metabolized by major
isoforms of CYP450

Amiadarone Fluvoxamine Phenacetin

Amitriptyline Haloperidol Phenformin

Carvedilol Imipramine Propafenone

Chloropromazine Indoramin Propanolol

Clomipramine Mefl oquine Quinidine

Clopidogrel Methoxyphenamine Risperidone

Clozapine Metoprolol Sertraline

Codeine Nortriptyline Tamadol

Desipramine Olanzapine Tamoxifen

Diltiazem Paroxetine Thioridazine

Encainide Perazine Timolol

Flencainide Perhexilene Tropisetron

Fluoxetine Perphenazine Venlafl axine

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Table 4.4 Commonly
prescribed medications,
which are metabolized
by CYP2D6

4 Pharmacogenetics