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

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. To identify the association between serum AMT and nortriptyline (NT) concentration and CYP2C19 pol...

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Published in:Digestive and liver disease 2021-11, Vol.53 (11), p.1422-1427
Main Authors: Zhou, Wen-cong, Jia, Lin, Deng, Qi, Wen, Yu-guan, Shang, De-wei, Ni, Xiao-jia, Huang, Yao-xing, Liu, Yao, Zhao, Han-bing, Yang, Meng, Dou, Guo-yuan
Format: Article
Language:English
Subjects:
Amitriptyline
Amitriptyline - administration & dosage
Amitriptyline - blood
Antidepressive Agents - administration & dosage
Antidepressive Agents - blood
CYP2C19
Cytochrome P-450 CYP2C19
Dose-Response Relationship, Drug
Female
Humans
IBS-D
Irritable Bowel Syndrome - drug therapy
Irritable Bowel Syndrome - genetics
Male
Middle Aged
Polymorphism, Single Nucleotide
Prospective Studies
Serum concentration
Severity of Illness Index
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Summary: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. To identify the association between serum AMT and nortriptyline (NT) concentration and CYP2C19 polymorphism and the clinical response in IBS-D patients. 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. 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. 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.
ISSN:1590-8658
1878-3562
DOI:10.1016/j.dld.2021.02.020