dc.creator | Feldman K. | |
dc.creator | Kearns G.L. | |
dc.creator | Pearce R.E. | |
dc.creator | Abdel-Rahman S.M. | |
dc.creator | Steven Leeder J. | |
dc.creator | Friesen A. | |
dc.creator | Staggs V.S. | |
dc.creator | Gaedigk A. | |
dc.creator | Weigel J. | |
dc.creator | Shakhnovich V. | |
dc.date.accessioned | 2022-09-26T18:58:47Z | |
dc.date.available | 2022-09-26T18:58:47Z | |
dc.date.issued | 2022 | |
dc.identifier.uri | https://doi.org/10.1111/cts.13232 | |
dc.identifier.uri | https://repository.tcu.edu/handle/116099117/55749 | |
dc.description.abstract | The 13C-pantoprazole breath test (PAN-BT) is a safe, noninvasive, in vivo CYP2C19 phenotyping probe for adults. Our objective was to evaluate PAN-BT performance in children, with a focus on discriminating individuals who, according to guidelines from the Clinical Pharmacology Implementation Consortium (CPIC), would benefit from starting dose escalation versus reduction for proton pump inhibitors (PPIs). Children (n = 65, 6–17 years) genotyped for CYP2C19 variants *2, *3, *4, and *17 received a single oral dose of 13C-pantoprazole. Plasma concentrations of pantoprazole and its metabolites, and changes in exhaled 13CO2 (termed delta-over-baseline or DOB), were measured 10 times over 8 h using high performance liquid chromatography with ultraviolet detection and spectrophotometry, respectively. Pharmacokinetic parameters of interest were generated and DOB features derived using feature engineering for the first 180 min postadministration. DOB features, age, sex, and obesity status were used to run bootstrap analysis at each timepoint (Ti) independently. For each iteration, stratified samples were drawn based on genotype prevalence in the original cohort. A random forest was trained, and predictive performance of PAN-BT was evaluated. Strong discriminating ability for CYP2C19 intermediate versus normal/rapid metabolizer phenotype was noted at DOBT30 min (mean sensitivity: 0.522, specificity: 0.784), with consistent model outperformance over a random or a stratified classifier approach at each timepoint (p < 0.001). With additional refinement and investigation, the test could become a useful and convenient dosing tool in clinic to help identify children who would benefit most from PPI dose escalation versus dose reduction, in accordance with CPIC guidelines. © 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. | |
dc.language | en | |
dc.publisher | Wiley | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | Clinical and Translational Science | |
dc.subject | cytochrome P450 2C19 | |
dc.subject | drug metabolite | |
dc.subject | pantoprazole | |
dc.subject | pantoprazole c 13 | |
dc.subject | radiopharmaceutical agent | |
dc.subject | unclassified drug | |
dc.subject | 2 [[(2 pyridyl)methyl]sulfinyl]benzimidazole derivative | |
dc.subject | CYP2C19 protein, human | |
dc.subject | cytochrome P450 2C19 | |
dc.subject | pantoprazole | |
dc.subject | proton pump inhibitor | |
dc.subject | adolescent | |
dc.subject | age distribution | |
dc.subject | area under the curve | |
dc.subject | Article | |
dc.subject | bootstrapping | |
dc.subject | breath analysis | |
dc.subject | child | |
dc.subject | cohort analysis | |
dc.subject | controlled study | |
dc.subject | drug blood level | |
dc.subject | drug clearance | |
dc.subject | drug dose escalation | |
dc.subject | drug dose reduction | |
dc.subject | female | |
dc.subject | gastroesophageal reflux | |
dc.subject | genetic variability | |
dc.subject | genotype | |
dc.subject | high performance liquid chromatography | |
dc.subject | human | |
dc.subject | major clinical study | |
dc.subject | male | |
dc.subject | obesity | |
dc.subject | pantoprazole c 13 breath test | |
dc.subject | patient selection | |
dc.subject | phenotype | |
dc.subject | practice guideline | |
dc.subject | prevalence | |
dc.subject | prospective study | |
dc.subject | random forest | |
dc.subject | sex difference | |
dc.subject | single drug dose | |
dc.subject | spectrophotometry | |
dc.subject | ultraviolet spectroscopy | |
dc.subject | adult | |
dc.subject | genetics | |
dc.subject | metabolism | |
dc.subject | procedures | |
dc.subject | 2-Pyridinylmethylsulfinylbenzimidazoles | |
dc.subject | Adult | |
dc.subject | Breath Tests | |
dc.subject | Child | |
dc.subject | Cytochrome P-450 CYP2C19 | |
dc.subject | Genotype | |
dc.subject | Humans | |
dc.subject | Pantoprazole | |
dc.subject | Proton Pump Inhibitors | |
dc.title | Utility of the 13C-pantoprazole breath test as a CYP2C19 phenotyping probe for children | |
dc.type | Article | |
dc.rights.holder | 2022 The Authors | |
dc.rights.license | CC BY-NC-ND 4.0 | |
local.college | Burnett School of Medicine | |
local.department | Burnett School of Medicine | |
local.persons | Kearns (SOM) | |