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The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client-owned dogs received a CRI of CA at a dose of 25 mg/m 2 /h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high-pressure liquid chromatography. The mean peak concentration (C MAX ) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 μg/mL and 11.39 ± 3.37 h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 μg/mL and 16.91 + 3.60 h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 μg/mL at both the 1- and 8-h time points. The steady-state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma., (© 2016 John Wiley & Sons Ltd.)

Intravenous benzodiazepines are utilized as first-line drugs to treat prolonged epileptic seizures in dogs and alternative routes of administration are required when venous access is limited. This study compared the pharmacokinetics of midazolam after intravenous (IV), intramuscular (IM), and rectal (PR) administration. Six healthy dogs were administered 0.2 mg/kg midazolam IV, IM, or PR in a randomized, 3-way crossover design with a 3-day washout between study periods. Blood samples were collected at baseline and at predetermined intervals until 480 min after administration. Plasma midazolam concentrations were measured by high-pressure liquid chromatography with UV detection. Rectal administration resulted in erratic systemic availability with undetectable to low plasma concentrations. Arithmetic mean values ± SD for midazolam peak plasma concentrations were 0.86 ± 0.36 μg/mL (C0) and 0.20 ± 0.06 μg/mL (Cmax), following IV and IM administration, respectively. Time to peak concentration (Tmax ) after IM administration was 7.8 ± 2.4 min with a bioavailability of 50 ± 16%. Findings suggest that IM midazolam might be useful in treating seizures in dogs when venous access is unavailable, but higher doses may be needed to account for intermediate bioavailability. Rectal administration is likely of limited efficacy for treating seizures in dogs., (© 2012 John Wiley & Sons Ltd.)

This crossover study compared the pharmacokinetics of cytarabine in six healthy dogs following intravenous constant rate infusion (CRI) and subcutaneous (SC) administrations, as these are two routes of administration commonly employed in the treatment of meningoencephalitis of unknown etiology. Each dog received a SC cytarabine injection of 50 mg/m(2) or an 8 h CRI of 25 mg/m(2) per hour, with a 7-day washout before receiving the alternative treatment. Blood samples were collected for 16 h after CRI initiation and for 8 h after SC injection. Plasma concentrations were measured by high-pressure liquid chromatography (HPLC). Pharmacokinetic parameters were estimated using the best-fit compartmental analysis for both CRI and SC routes. Terminal half-life (T(1/2) ) of cytarabine was 1.35 ± 0.3 and 1.15 ± 0.13 h after SC administration and CRI, respectively. Mean peak concentration (Cmax ) was 2.88 and 2.80 μg/mL for SC and CRI administration, respectively. Volume of distribution was 0.66 ± 0.07 l/kg. The 8-h CRI produced steady-state plasma concentrations as determined by consecutive measurement that did not decline until the end of the infusion. The SC administration did not achieve steady-state concentrations because cytarabine administered by this route was rapidly absorbed and eliminated quickly. The steady state achieved with the cytarabine CRI may produce a more prolonged exposure of cytarabine at cytotoxic levels in plasma compared to the concentrations after SC administration., (© 2012 John Wiley & Sons Ltd.)

Levetiracetam (LEV) is a commonly used add-on medication in dogs with refractory epilepsy. The objective of this study was to determine if the pharmacokinetics of LEV are altered by concurrent administration of phenobarbital (PB). Six healthy dogs received a single oral dose of LEV (16.7-27.8 mg/kg). Blood samples were collected at baseline and intermittently for 24 h. The study was repeated after the dogs received oral PB (2.0-3.3 mg/kg) twice daily for 21 days. Plasma LEV levels were evaluated by high pressure liquid chromatography, and data analyzed using a compartmental model. Compared with values determined when LEV was administered alone, concurrent administration of PB resulted in a decrease in LEV peak concentration (C(max) ) from 32.39 ± 6.76 to 18.22 ± 8.97 (P = 0.0071), a decrease in elimination half-life (T(1/2) ) from 3.43 ± 0.47 to 1.73 ± 0.22 (P = 0.0005), and an increase in oral clearance from 124.93 ± 26.93 to 252.99 ± 135.43 ml/h/kg (P < 0.0001). Concurrent PB administration significantly alters the pharmacokinetics of LEV in the dog, indicating that dosage adjustments might be necessary when the drug is administered with PB., (© 2010 Blackwell Publishing Ltd.)