Document Type

Article

Publication Date

3-2026

Identifier

DOI: 10.1111/cts.70523

Abstract

Real-world data investigating CYP2D6 on the efficacy of ondansetron for nausea and vomiting in pregnancy (NVP) is lacking. Evidence shows CYP2D6 ultrarapid metabolizers are at risk of ondansetron nonresponse due to increased metabolism. We conducted a retrospective cohort study of early pregnant patients on ondansetron for NVP. Genotype data for 11 CYP2D6 variants and copy number variations were translated into activity score (AS) and metabolizer status: poor (PM), intermediate (IM), normal (NM), and ultrarapid (UM) metabolizers. A total of 264 women met inclusion/exclusion criteria (99 cases and 165 controls). Multivariate regression analyses of metabolizer status and AS were adjusted for significant independent variables. The majority had gravidity of two, singleton pregnancy, a median age of 28 (interquartile range [IQR] 24-31) years, and identified as White (65.5%). Ondansetron dose was similar among the cohort and half received other antiemetics simultaneously. Clinical characteristics between cases and controls did not differ except for gestational age (8 vs. 10 weeks, p = 0.004) and primigravida rate (45.5% vs. 32.7%, p = 0.017). When adjusted for covariates, metabolizer status was not associated with response. UM/NM had non-significantly higher risk of nonresponse (odds ratio [OR] 1.53, 95% confidence interval [CI], 0.88-2.66) compared to PM/IM. Similar trends were observed with higher CYP2D6 AS showing increased risk of nonresponse (OR 1.22, 95% CI [0.81-1.85]). This study found no significant differences in ondansetron response in early pregnancy based on CYP2D6 UM/NM versus PM/IM and AS. Additional prospective investigations are necessary to confirm the CYP2D6 effect on ondansetron efficacy in pregnant patients.

Journal Title

Clin Transl Sci

Volume

19

Issue

3

First Page

70523

Last Page

70523

MeSH Keywords

Humans; Female; Ondansetron; Cytochrome P-450 CYP2D6; Pregnancy; Adult; Retrospective Studies; Case-Control Studies; Antiemetics; Young Adult; Treatment Outcome; Morning Sickness; Genotype; Vomiting; Nausea

PubMed ID

41820792

Keywords

CYP2D6; genotyping; nausea and vomiting; personalized medicine; pharmacogenetics; precision medicine; pregnancy; women

Comments

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Publisher's Link: https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.70523

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