{"title":"在酶和钒酸盐氧化试验中，依曲巴格诱导的胆红素浓度错误升高：血清依曲巴格高浓度的介入。","authors":"Shun Oda, Kosuke Doki, Naoshi Obara, Yoshiharu Suzuki, Shigeru Chiba, Masato Homma","doi":"10.1097/FTD.0000000000001307","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The administration of eltrombopag, used to restore low blood count, demonstrates a positive interference of blood bilirubin levels when analyzed through the diazo assay. However, research on bilirubin measurements using other methods is limited. Therefore, using an enzymatic assay, this study aimed to investigate the effect of serum eltrombopag on bilirubin measurements in patients with aplastic anemia. It further assessed the concentration-dependent effect of eltrombopag on bilirubin measurements using enzymatic and vanadate oxidation assays.</p><p><strong>Methods: </strong>Total and conjugated bilirubin concentrations measured using an enzymatic assay and serum eltrombopag concentrations were examined in 227 serum samples collected from 30 patients with aplastic anemia receiving eltrombopag. Eltrombopag-spiked samples were analyzed using the enzymatic and vanadate oxidation assays for total and conjugated bilirubin to determine its concentration-dependent effects.</p><p><strong>Results: </strong>A strong positive correlation was observed between total bilirubin and serum eltrombopag concentrations in patients receiving eltrombopag (r = 0.820). However, the correlation between conjugated bilirubin and serum eltrombopag concentrations was weaker (r = 0.413). In eltrombopag-spiked serum samples, the enzymatic assay showed significant false elevation of total bilirubin concentrations at ≥6.0 mcg/mL; no interference with conjugated bilirubin measurements was observed. The vanadate oxidation assay showed mild positive biases of 0.2 and 0.1 mg/dL for total and conjugated bilirubin concentrations, respectively, at a high eltrombopag concentration (50 mcg/mL).</p><p><strong>Conclusions: </strong>Eltrombopag causes clinically significant concentration-dependent interference in total blood bilirubin, but not in conjugated bilirubin measurements through the enzymatic assay in patients with aplastic anemia. The vanadate oxidation assay may be used as an alternative to measure total blood bilirubin when the eltrombopag concentration is below 50 mcg/mL.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Eltrombopag-Induced Falsely Elevated Bilirubin Concentrations in Enzymatic and Vanadate Oxidation Assays: Involvement of High Serum Eltrombopag Concentrations.\",\"authors\":\"Shun Oda, Kosuke Doki, Naoshi Obara, Yoshiharu Suzuki, Shigeru Chiba, Masato Homma\",\"doi\":\"10.1097/FTD.0000000000001307\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The administration of eltrombopag, used to restore low blood count, demonstrates a positive interference of blood bilirubin levels when analyzed through the diazo assay. However, research on bilirubin measurements using other methods is limited. Therefore, using an enzymatic assay, this study aimed to investigate the effect of serum eltrombopag on bilirubin measurements in patients with aplastic anemia. It further assessed the concentration-dependent effect of eltrombopag on bilirubin measurements using enzymatic and vanadate oxidation assays.</p><p><strong>Methods: </strong>Total and conjugated bilirubin concentrations measured using an enzymatic assay and serum eltrombopag concentrations were examined in 227 serum samples collected from 30 patients with aplastic anemia receiving eltrombopag. Eltrombopag-spiked samples were analyzed using the enzymatic and vanadate oxidation assays for total and conjugated bilirubin to determine its concentration-dependent effects.</p><p><strong>Results: </strong>A strong positive correlation was observed between total bilirubin and serum eltrombopag concentrations in patients receiving eltrombopag (r = 0.820). However, the correlation between conjugated bilirubin and serum eltrombopag concentrations was weaker (r = 0.413). In eltrombopag-spiked serum samples, the enzymatic assay showed significant false elevation of total bilirubin concentrations at ≥6.0 mcg/mL; no interference with conjugated bilirubin measurements was observed. The vanadate oxidation assay showed mild positive biases of 0.2 and 0.1 mg/dL for total and conjugated bilirubin concentrations, respectively, at a high eltrombopag concentration (50 mcg/mL).</p><p><strong>Conclusions: </strong>Eltrombopag causes clinically significant concentration-dependent interference in total blood bilirubin, but not in conjugated bilirubin measurements through the enzymatic assay in patients with aplastic anemia. The vanadate oxidation assay may be used as an alternative to measure total blood bilirubin when the eltrombopag concentration is below 50 mcg/mL.</p>\",\"PeriodicalId\":23052,\"journal\":{\"name\":\"Therapeutic Drug Monitoring\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-02-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Therapeutic Drug Monitoring\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/FTD.0000000000001307\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICAL LABORATORY TECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Drug Monitoring","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/FTD.0000000000001307","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICAL LABORATORY TECHNOLOGY","Score":null,"Total":0}
Eltrombopag-Induced Falsely Elevated Bilirubin Concentrations in Enzymatic and Vanadate Oxidation Assays: Involvement of High Serum Eltrombopag Concentrations.
Background: The administration of eltrombopag, used to restore low blood count, demonstrates a positive interference of blood bilirubin levels when analyzed through the diazo assay. However, research on bilirubin measurements using other methods is limited. Therefore, using an enzymatic assay, this study aimed to investigate the effect of serum eltrombopag on bilirubin measurements in patients with aplastic anemia. It further assessed the concentration-dependent effect of eltrombopag on bilirubin measurements using enzymatic and vanadate oxidation assays.
Methods: Total and conjugated bilirubin concentrations measured using an enzymatic assay and serum eltrombopag concentrations were examined in 227 serum samples collected from 30 patients with aplastic anemia receiving eltrombopag. Eltrombopag-spiked samples were analyzed using the enzymatic and vanadate oxidation assays for total and conjugated bilirubin to determine its concentration-dependent effects.
Results: A strong positive correlation was observed between total bilirubin and serum eltrombopag concentrations in patients receiving eltrombopag (r = 0.820). However, the correlation between conjugated bilirubin and serum eltrombopag concentrations was weaker (r = 0.413). In eltrombopag-spiked serum samples, the enzymatic assay showed significant false elevation of total bilirubin concentrations at ≥6.0 mcg/mL; no interference with conjugated bilirubin measurements was observed. The vanadate oxidation assay showed mild positive biases of 0.2 and 0.1 mg/dL for total and conjugated bilirubin concentrations, respectively, at a high eltrombopag concentration (50 mcg/mL).
Conclusions: Eltrombopag causes clinically significant concentration-dependent interference in total blood bilirubin, but not in conjugated bilirubin measurements through the enzymatic assay in patients with aplastic anemia. The vanadate oxidation assay may be used as an alternative to measure total blood bilirubin when the eltrombopag concentration is below 50 mcg/mL.
期刊介绍：
Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.
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