Pharmacogenomic testing for CYP2C19 and CYP2D6 in cyclic vomiting syndrome

Area of Science:

• Pharmacogenomics
• Gastroenterology
• Clinical Pharmacology

Background:

• Amitriptyline (AT) is a first-line treatment for cyclic vomiting syndrome (CVS), but side effects often limit its use.
• Current dosing relies on trial and error, despite Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines recommending genotype-based dosing for AT.
• Genetic variations in CYP2C19 and CYP2D6 enzymes influence AT metabolism.

Purpose of the Study:

• To investigate the association between CYP2C19 and CYP2D6 genotypes and adverse drug reactions (ADRs), clinical response, and serum concentrations of AT and its metabolite, nortriptyline, in adults with CVS.
• To assess the potential utility of pharmacogenetic testing in managing CVS.

Main Methods:

• Pilot study involving 46 adults diagnosed with CVS.
• Determination of CYP2C19 and CYP2D6 genotypes.
• Analysis of the correlation between genotypes, ADRs, clinical response, and serum drug levels.

Main Results:

• Prevalence of genetic variations: 33% normal CYP2C19, 4% poor, 43% ultrarapid; 61% normal CYP2D6, 9% poor, 2% ultrarapid.
• No statistically significant association was found between genotype and ADRs, clinical response, or serum drug concentration.
• A trend towards significance was observed between CYP2D6 genotype and clinical response (p=0.06).
• Adverse drug reactions (ADRs) occurred in 46% of patients, leading to discontinuation in 28%.

Conclusions:

• A notable subset of CVS patients possess dysfunctional CYP2C19 and CYP2D6 alleles.
• Larger prospective studies are required to confirm the clinical impact of pharmacogenomic testing in CVS.
• Pharmacogenomic testing holds potential for optimizing AT therapy, predicting ADRs, and enabling personalized treatment strategies for CVS.