Doxorubicin area under the curve is an important predictor of neutropenia in dogs with naturally occurring cancers

Luke Anthony Wittenburg, Kristen Weishaar, Dominique Ramirez, Daniel L. Gustafson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Doxorubicin (DOX) area-under-the-curve (AUC) was calculated for 40 dogs with spontaneously occurring cancers using a previously validated limited-sampling approach. All dogs were administered a dose of 30 mg/m2 by intravenous infusion and serum samples were collected at 5, 45 and 60 minutes post-infusion. DOX and its major metabolite, doxorubicinol (doxol), were quantified in serum samples using high-performance liquid chromatography tandem-mass spectrometry. Wide interpatient variability was observed in the predicted DOX AUC with a coefficient of variation of 34%. A significant relationship was found between DOX AUC and absolute white blood cell count (P = 0.003), absolute neutrophil count (ANC; P = 0.002) and surviving fraction of neutrophils (P = 0.03) approximately 1 week after dosing (nadir). No changes in other hematologic parameters (red blood cells, platelets, lymphocytes, haemoglobin) were found to correlate with DOX AUC. The absolute dose (mg) and the dose per unit body weight (mg/kg) were not significantly correlated with nadir ANC. No relationships were found between maximum serum doxol concentration and myelosuppression. Baseline ANC was also significantly correlated to nadir ANC and a model was constructed using baseline ANC and DOX AUC that significantly described the nadir ANC. These findings demonstrate the important relationship between systemic DOX exposure and degree of neutropenia in dogs, and suggest a potential for individualized, pharmacokinetically-guided DOX dosing in dogs.

Original languageEnglish (US)
JournalVeterinary and Comparative Oncology
DOIs
StatePublished - Jan 1 2019

Fingerprint

neutropenia
doxorubicin
Neutropenia
Doxorubicin
Area Under Curve
Dogs
neoplasms
dogs
Neoplasms
neutrophils
Neutrophils
Serum
administered dose
dosage
Tandem Mass Spectrometry
Leukocyte Count
leukocyte count
Intravenous Infusions
sampling
hemoglobin

Keywords

  • canine cancer
  • doxorubicin
  • limited-sampling model
  • pharmacokinetic-pharmacodynamic relationship

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Doxorubicin area under the curve is an important predictor of neutropenia in dogs with naturally occurring cancers. / Wittenburg, Luke Anthony; Weishaar, Kristen; Ramirez, Dominique; Gustafson, Daniel L.

In: Veterinary and Comparative Oncology, 01.01.2019.

Research output: Contribution to journalArticle

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