The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5-2 mg kg day ). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 μg/ml. The population estimate (CV%) for elimination half-life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 μg/ml at the 30-, 60-, 90-, and 120-min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.
Background: Cytarabine (CA) is used to treat dogs with meningoencephalitis of unknown etiology (MUE) by subcutaneous or intravenous administration.
Aim: The objective was to investigate transdermal iontophoresis and rectal administration as alternative routes of CA delivery.
Methods: Two client-owned dogs with MUE were studied. The ActivaPatch® IONTOGOTM 12.0 iontophoresis drug delivery system delivered 200 mg/m2 CA transdermally. Blood samples were collected by sparse sampling technique after initiation of the device. At another visit, 100 mg/m2 CA was administered rectally. Blood samples were collected by sparse sampling technique after administration. Plasma CA concentrations were measured by high-pressure liquid chromatography.
Results: The concentration of plasma CA after transdermal and rectal administration was below the limits of quantification (0.1 μg/ml) in all samples suggesting inadequate bioavailability with transdermal and rectal administration.
Conclusion: Transdermal and rectal CA administration are not reasonable alternative routes of delivery.
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