Bioassay and liquid chromatography-mass spectrometry are not equivalent in itraconazole therapeutic drug monitoring in dogs.

IF 1.6 3区农林科学 Q2 VETERINARY SCIENCES

American journal of veterinary research Pub Date : 2026-09-08 DOI:10.2460/ajvr.26.07.0303

Kelly Hearn, Arnon Gal, Nathan P Wiederhold, Sunam Park, Andrew Hanzlicek, Jennifer M Reinhart

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引用次数: 0

Abstract

Objective: To compare itraconazole therapeutic drug monitoring (TDM) results by culture-based bioassay versus liquid chromatography-mass spectrometry (LC-MS) in dogs with blastomycosis and determine how the choice of assay might influence dosage adjustments.

Methods: This was a retrospective study. Ninety-seven samples from 14 client-owned dogs with blastomycosis were collected from October 2023 through May 2025 and analyzed by bioassay and 3 LC-MS-derived variables: itraconazole alone (ITZ), the hydroxyitraconazole metabolite, and the sum of itraconazole and hydroxyitraconazole. Linear mixed models were used to assess the relationship between dosage and itraconazole concentration by bioassay and LC-MS and between bioassay and the LC-MS variables. A clinical concordance grid was used to assess agreement between bioassay and ITZ by LC-MS regarding dosage-adjustment decisions.

Results: There was no significant association between itraconazole dosage and serum concentration. There was a significant relationship between concentration by bioassay versus LC-MS (P < .01). The association was weak for ITZ (r2 = 0.40) but was moderate for the hydroxyitraconazole metabolite (r2 = 0.48) and the sum of itraconazole and hydroxyitraconazole (r2 = 0.48). Of 97 samples, 62 (64%) demonstrated agreement in dosage adjustment, and 35 (36%) did not.

Conclusions: Dosage of itraconazole does not reliably predict serum itraconazole concentration, requiring TDM for effective dosage-adjustment decisions. Bioassay and LC-MS are not interchangeable assays for itraconazole TDM in dogs.

Clinical relevance: TDM should be considered during long-term itraconazole therapy to optimize dose. A single assay method (bioassay or LC-MS) should be used consistently throughout the entire course of antifungal therapy.

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生物测定法和液相色谱-质谱法在伊曲康唑治疗药物监测中并不等同。

目的：比较伊曲康唑治疗药物监测（TDM）中培养生物测定法与液相色谱-质谱法（LC-MS）对芽孢菌病犬的监测结果，并探讨测定方法的选择对剂量调整的影响。方法：回顾性研究。从2023年10月至2025年5月，从14只患有芽孢菌病的客户犬中采集了97份样本，采用生物测定法和lc - ms衍生的3个变量：伊曲康唑（ITZ）、羟基伊曲康唑代谢物、伊曲康唑和羟基伊曲康唑的总和。采用线性混合模型评估伊曲康唑剂量与生物测定和LC-MS浓度之间的关系，以及生物测定和LC-MS变量之间的关系。临床一致性网格用于评估生物测定法和LC-MS在剂量调整决策方面的一致性。结果：伊曲康唑剂量与血清浓度无显著相关性。生物测定浓度与LC-MS浓度之间存在显著相关性（P < 0.01）。ITZ的相关性较弱（r2 = 0.40），羟基伊曲康唑代谢物的相关性中等（r2 = 0.48），伊曲康唑和羟基伊曲康唑的总和的相关性中等（r2 = 0.48）。在97份样本中，62份（64%）显示剂量调整一致，35份（36%）不一致。结论：伊曲康唑的剂量不能可靠地预测伊曲康唑的血清浓度，需要TDM进行有效的剂量调整决策。伊曲康唑TDM的生物测定和LC-MS不能互换。临床意义：长期伊曲康唑治疗应考虑TDM，以优化剂量。在整个抗真菌治疗过程中应始终使用单一的测定方法（生物测定法或LC-MS）。

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来源期刊

American journal of veterinary research 农林科学-兽医学

CiteScore

1.70

自引率

10.00%

发文量

186

审稿时长

3 months

期刊介绍： The American Journal of Veterinary Research supports the collaborative exchange of information between researchers and clinicians by publishing novel research findings that bridge the gulf between basic research and clinical practice or that help to translate laboratory research and preclinical studies to the development of clinical trials and clinical practice. The journal welcomes submission of high-quality original studies and review articles in a wide range of scientific fields, including anatomy, anesthesiology, animal welfare, behavior, epidemiology, genetics, heredity, infectious disease, molecular biology, oncology, pharmacology, pathogenic mechanisms, physiology, surgery, theriogenology, toxicology, and vaccinology. Species of interest include production animals, companion animals, equids, exotic animals, birds, reptiles, and wild and marine animals. Reports of laboratory animal studies and studies involving the use of animals as experimental models of human diseases are considered only when the study results are of demonstrable benefit to the species used in the research or to another species of veterinary interest. Other fields of interest or animals species are not necessarily excluded from consideration, but such reports must focus on novel research findings. Submitted papers must make an original and substantial contribution to the veterinary medicine knowledge base; preliminary studies are not appropriate.