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

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/m(2) IV over 24 h), followed by a SC protocol (50 mg/m(2) 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 mu g/ml, range 1.60-9.70 mu g/ml) was significantly higher than the CRI (1.09 mu g/ml, range 0.77-1.67 mu g/ml; p = .02). Median concentration at 1h and 8h following initiation of treatment was significantly higher for the SC protocol (CA(1) 2.28 mu g/ml, range 0.97-2.67; CA(8) 1.83 mu g/ml, range 0.77-2.84) compared to the CRI (CA1 0.01 mu g/ml, range 0-0.45; CA(8) 0.74 mu g/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/m(2) 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.

Automated summary

This study compared the pharmacokinetics of subcutaneous (SC) and constant rate infusion (CRI) protocols of cytosine arabinoside (CA) in dogs with meningoencephalomyelitis of unknown aetiology (MUE). The SC protocol showed significantly higher peak CA concentration and sustained levels compared to the CRI protocol, with higher concentrations observed at 1h and 8h following treatment initiation.