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Background <p>Doxorubicin (DOX) is an anthracycline chemotherapeutic used for many canine malignancies, and its adverse event (AE) profile has been well-described in dogs. A limited sampling (LS) pharmacokinetic model was recently developed in canine patients to predict hematologic exposure to DOX. The primary goal of this study was to evaluate within-patient and between-patient variability in DOX exposure over three consecutive doses using the LS model. A secondary goal was to determine if there is a correlation between DOX exposure and gastrointestinal (GI) AEs utilizing a standardized owner questionnaire.</p> Methods <p>We performed a prospective evaluation of DOX exposure in seven tumor-bearing dogs across three cycles of treatment and compared the coefficient of variation (%CV) of the between- and within-patient exposures.</p> Results <p>This data set corroborated the ability of the DOX LS model to predict absolute neutrophil count for patients whose absolute neutrophil counts are lower at seven days compared to baseline. Dose normalized within-patient variability (4.7%) was significantly lower (<i>p</i> &lt; 0.001) than between-patient variability (25.4%) in DOX exposure. Decreased appetite (<i>p</i> = 0.005) and increased nausea (<i>p</i> = 0.02) were significantly correlated with DOX exposure.</p> Conclusions <p>Together, these data suggest wide interpatient variability in dose-normalized DOX exposure but much more consistent exposure within an individual patient across treatment cycles. Future studies can attempt to target specific DOX exposures and absolute neutrophil counts to assess if DOX dosing can be personalized to increase efficacy and decrease GI AEs.</p>

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Comparison of interpatient and intrapatient variability in doxorubicin exposure using a validated limited sampling model in dogs with cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月8日

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  • Sridhar Madan Veluvolu,
  • Robert B. Rebhun,
  • Jaeyoung Kim,
  • Luke Anthony Wittenburg

摘要

Background

Doxorubicin (DOX) is an anthracycline chemotherapeutic used for many canine malignancies, and its adverse event (AE) profile has been well-described in dogs. A limited sampling (LS) pharmacokinetic model was recently developed in canine patients to predict hematologic exposure to DOX. The primary goal of this study was to evaluate within-patient and between-patient variability in DOX exposure over three consecutive doses using the LS model. A secondary goal was to determine if there is a correlation between DOX exposure and gastrointestinal (GI) AEs utilizing a standardized owner questionnaire.

Methods

We performed a prospective evaluation of DOX exposure in seven tumor-bearing dogs across three cycles of treatment and compared the coefficient of variation (%CV) of the between- and within-patient exposures.

Results

This data set corroborated the ability of the DOX LS model to predict absolute neutrophil count for patients whose absolute neutrophil counts are lower at seven days compared to baseline. Dose normalized within-patient variability (4.7%) was significantly lower (p < 0.001) than between-patient variability (25.4%) in DOX exposure. Decreased appetite (p = 0.005) and increased nausea (p = 0.02) were significantly correlated with DOX exposure.

Conclusions

Together, these data suggest wide interpatient variability in dose-normalized DOX exposure but much more consistent exposure within an individual patient across treatment cycles. Future studies can attempt to target specific DOX exposures and absolute neutrophil counts to assess if DOX dosing can be personalized to increase efficacy and decrease GI AEs.