Pharmacokinetics of a cytosine arabinoside subcutaneous protocol in dogs with meningoencephalomyelitis of unknown aetiology

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Abstract

Cytosine arabinoside (CA) is a commonly used treatment for dogs with meningoencephalomyelitis of unknown aetiology (MUE) with various proposed protocols, many requiring 24 hours (h) of hospitalization or two visits within 24 h. This is a unidirectional study evaluating the pharmacokinetics of a CA subcutaneous (SC) protocol and a standard constant rate infusion (CRI) protocol in 8 dogs with MUE. Dogs received the CRI (200 mg/m2 IV over 24 h), followed by a SC protocol (50 mg/m2 every 2 h for 4 treatments) four weeks later. Plasma CA concentrations were measured by high-pressure liquid chromatography–tandem mass spectrometry (HPLC-MS). Median peak CA concentration for the SC protocol (3.40 µg/ml, range 1.60–9.70 µg/ml) was significantly higher than the CRI (1.09 µg/ml, range 0.77–1.67 µg/ml; p =.02). Median concentration at 1h and 8h following initiation of treatment was significantly higher for the SC protocol (CA1 2.28 µg/ml, range 0.97–2.67; CA8 1.83 µg/ml, range 0.77–2.84) compared to the CRI (CA1 0.01 µg/ml, range 0–0.45; CA8 0.74 µg/ml, range 0.67–1.11; p =.01). While the PK properties of CA when administered as a CRI has been previously investigated, this study demonstrated that CA when administered via repeated 50 mg/m2 injections every 2 h over an 8-h period, provided sustained plasma levels above its therapeutic target and for a significantly longer duration of time than did a standard CRI protocol.

Original languageEnglish (US)
Pages (from-to)696-704
Number of pages9
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume44
Issue number5
DOIs
StatePublished - Sep 2021

Keywords

  • MUE
  • MUO
  • canine
  • chemotherapy
  • immunosuppression

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

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