Pharmacokinetics of a cytosine arabinoside subcutaneous protocol in dogs with meningoencephalomyelitis of unknown aetiology
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 (CA12.28 µg/ml, range 0.97–2.67; CA81.83 µg/ml, range 0.77–2.84) compared to the CRI (CA1 0.01 µg/ml, range 0–0.45; CA80.74 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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:44 |
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| Enthalten in: |
Journal of Veterinary Pharmacology and Therapeutics - 44(2021), 5, Seite 696-704 |
| Beteiligte Personen: |
Levitin, Hilary A. [VerfasserIn] |
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| BKL: |
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| Anmerkungen: |
Copyright 2021 John Wiley & Sons Ltd |
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| Umfang: |
9 |
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| doi: |
10.1111/jvp.12980 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Pharmacokinetics of a cytosine arabinoside subcutaneous protocol in dogs with meningoencephalomyelitis of unknown aetiology |
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| 520 | |a 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 (CA12.28 µg/ml, range 0.97–2.67; CA81.83 µg/ml, range 0.77–2.84) compared to the CRI (CA1 0.01 µg/ml, range 0–0.45; CA80.74 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. | ||
| 700 | 1 | |a Foss, Kari D. |4 aut | |
| 700 | 1 | |a Li, Zhong |4 aut | |
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| 700 | 1 | |a Fan, Timothy M. |4 aut | |
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