165 Cyp3a5 Contribution to Budesonide Treatment Failure in Children With Eosinophilic Esophagitis

Chevalier, Rachel; Shakhnovich, Valentina; Gaedigk, Roger; Pirani, Karim; Noel-Macdonnell, Janelle R

doi:10.1016/s0016-5085(21)00842-8

Cited by 1 publication

(1 citation statement)

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“…GI inflammation, through its downregulation of CYP3A expression [103] and function [104] locally, may contribute to higher systemic exposure of orally administered budesonide [105,106]. Small, preliminary studies also indicate that the CYP3A5 genotype may contribute to budesonide treatment failure in eosinophilic esophagitis for patients with wild-type alleles who may metabolize the drug too quickly [107]. Further studies evaluating the contribution of the CYP3A5 genotype, ABCB1 genotype, and esophageal inflammation on the treatment of GI diseases with budesonide are under way.…”

Section: Corticosteroidsmentioning

confidence: 99%

Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug–Gene Pairs to Know

Sandritter,

Chevalier,

Abt

et al. 2023

Pharmaceuticals

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Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (TPMT) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic testing has become more readily available for other genes relevant to drug dose individualization. Common medications prescribed by gastroenterologists for conditions other than inflammatory bowel disease now have actionable guidelines, which can improve medication efficacy and safety; however, a clear understanding of how to interpret the results remains a challenge for many clinicians, precluding wide implementation of genotype-guided dosing for drugs other than 6-mercaptopurine and azathioprine. Our goal is to provide a practical tutorial on the currently available pharmacogenetic testing options and a results interpretation for drug–gene pairs important to medications commonly used in pediatric gastroenterology. We focus on evidence-based clinical guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC®) to highlight relevant drug–gene pairs, including proton pump inhibitors and selective serotonin reuptake inhibitors and cytochrome P450 (CYP) 2C19, ondansetron and CYP2D6, 6-mercaptopurine and TMPT and Nudix hydrolase 15 (NUDT15), and budesonide and tacrolimus and CYP3A5.

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