Role of serum amitriptyline concentration and CYP2C19 polymorphism in predicting the response to low-dose amitriptyline in irritable bowel syndrome

Abstract

Background: Low-dose amitriptyline (AMT) is an effective treatment for diarrhea-dominant irritable bowel syndrome (IBS-D). Its efficacy depends upon its serum concentration and the patient's CYP2C19 genotype.

Aims: To identify the association between serum AMT and nortriptyline (NT) concentration and CYP2C19 polymorphism and the clinical response in IBS-D patients.

Methods: Ninety IBS-D patients were treated of AMT for 6 weeks. Efficacy was evaluated by the results of the Adequate Relief question each week and an IBS severity scoring system (IBS-SSS) at 0, 3, and 6 weeks. CYP2C19 genotyping was performed by direct sequencing. AMT and NT steady-state serum concentrations were detected by high-performance liquid chromatography.

Results: The CYP2C19 polymorphism exhibited a significant influence on the NT serum concentration but did not predict the clinical efficacy of AMT for treating IBS-D. The NT steady-state and dose-corrected serum concentrations were significantly correlated with an improvement in the IBS-SSS score after 6 weeks, whereas the AMT serum concentration was not correlated with clinical improvement. The cut-off NT steady-state serum concentration of 2.91 ng/ml may help distinguish responders from non-responders.

Conclusions: NT serum concentration but not CYP2C19 polymorphism may be correlated with the clinical efficacy of AMT for treating IBS-D, and such a response may occur at the upper NT threshold of 2.91 ng/ml.

Keywords: Amitriptyline; CYP2C19; IBS-D; Serum concentration.