Plasma and urine pharmacokinetics of two formulations of dexamethasone in greyhound dogs.

Dexamethasone, formulated as sodium phosphate and as phenylpropionate combined with sodium phosphate, was administered subcutaneously to six greyhounds. Plasma and urine were collected for up to 240 h and analysed with a limit of quantification (LOQ) of at least 100 pg/ml for dexamethasone. Dexamethasone, formulated as sodium phosphate, terminal half-life was 10.4 h in plasma and approximately 16 h in urine, and at 96 h, plasma hydrocortisone concentrations returned to background with dexamethasone levels around the LOQ. Dexamethasone, formulated as phenylpropionate combined with sodium phosphate, terminal half-life, was 25.6 h in plasma and approximately 26 h in urine, and at 96 h, plasma hydrocortisone concentrations returned to background with dexamethasone levels in three of the six greyhounds around the LOQ. Critical assessment of the pharmacokinetic and pharmacodynamic data indicated how it might be utilized for medication control in racing greyhounds.

Plasma and urine pharmacokinetics of intravenously administered flunixin in greyhound dogs.

Medication control in greyhound racing requires information from administration studies that measure drug levels in the urine as well as plasma, with time points that extend into the terminal phase of excretion. To characterize the plasma and the urinary pharmacokinetics of flunixin and enable regulatory advice for greyhound racing in respect of both medication and residue control limits, flunixin meglumine was administered intravenously on one occasion to six different greyhounds at the label dose of 1 mg/kg and the levels of flunixin were measured in plasma for up to 96 hr and in urine for up to 120 hr. Using the standard methodology for medication control, the irrelevant plasma concentration was determined as 1 ng/ml and the irrelevant urine concentration was determined as 30 ng/ml. This information can be used by regulators to determine a screening limit, detection time and a residue limit. The greyhounds with the highest average urine pH had far greater flunixin exposure compared with the greyhounds that had the lowest. This is entirely consistent with the extent of ionization predicted by the Henderson-Hasselbalch equation. This variability in the urine pharmacokinetics reduces with time, and at 72 hr postadministration, in the terminal phase, the variability in urine and plasma flunixin concentrations are similar and should not affect medication control.

The pharmacokinetics of orally administered butylscopolamine in greyhound dogs.

The oral tablet formulation of butylscopolamine, which is available without prescription, is commonly used by trainers of racing greyhounds to treat functional urethral obstruction. As medication control of butylscopolamine is therefore required for such use to ensure the integrity of greyhound racing, an administration study was performed in six greyhounds to determine the pharmacokinetics of orally administered butylscopolamine. A single dose of one 10 mg butylscopolamine tablet was administered orally to simulate this use in greyhound racing. Blood, urine and faeces were collected at regular intervals from the greyhounds for up to 9 days and butylscopolamine concentrations determined. There was some, but very limited, absorption of butylscopolamine, with rapid elimination from plasma with a mean half-life of 2 hr. Urine concentrations initially declined in a similar manner to the plasma pharmacokinetics but then entered a much longer half-life of approximately 50 hr. Faecal concentrations declined to very low levels between 48 and 120 hr. The use of orally administered butylscopolamine for functional urethral obstruction in greyhounds is unjustified due to this very limited drug absorption. Medication control of butylscopolamine's antispasmodic effect on the digestive tract is possible by setting screening limits based on the urinary and faecal drug levels as determined in this study.

Efficacy and safety of sarolaner (Simparica®) in the treatment and control of naturally occurring flea infestations in dogs presented as veterinary patients in Australia.

BACKGROUND: The efficacy and safety of a novel isoxazoline compound, sarolaner (Simparica®, Zoetis) and spinosad (Comfortis®, Elanco) as a positive control were evaluated for the treatment and control of natural flea infestations on dogs in two randomised, blinded, multi-centric clinical trials conducted in 11 veterinary clinics in northeastern and southeastern states of Australia. METHODS: A total of 162 client-owned dogs (80 in northern study and 82 in southern study) from 105 households were enrolled. Each household was randomly allocated to receive either sarolaner (Simparica®, Zoetis) or spinosad (Comfortis®, Elanco). Dogs were dosed on Days 0, 30 and 60 and physical examinations and flea counts were conducted on Days 0, 14, 30, 60 and 90. Efficacy assessments were based on the percentage reduction in live flea counts post-treatment compared to Day 0. RESULTS: In the northern study, at enrolment, primary dogs had flea counts ranging from 5 to 772. At the first efficacy assessment on Day 14, sarolaner resulted in 99.3% mean reduction in live flea counts relative to Day 0, compared to 94.6% in the spinosad group. On Day 30, the sarolaner-treated group had mean efficacy of 99.2% compared to 95.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.8%. In the southern study, at enrolment, primary dogs had flea counts ranging from 5 to 156. Both sarolaner and spinosad resulted in ≥ 96.7% mean reduction in live flea counts on Day 14. On Day 30, the sarolaner-treated group had mean efficacy of 99.5% compared to 89.7% in the spinosad-treated group, and on days 60 and 90, both groups had mean efficacies of ≥ 98.6%. No treatment-related adverse events were observed in either study. CONCLUSIONS: A single monthly dose of sarolaner (Simparica®) administered orally at 2-4 mg/kg for three consecutive months was well tolerated and provided excellent efficacy against natural infestations of fleas under a range of Australian field conditions including different climatic and housing conditions. Similar efficacy was observed with spinosad (Comfortis®) after the second and third monthly treatments.

Evaluation of the effectiveness of a novel oral formulation of sarolaner (Simparica™) for the treatment and control of fleas on dogs.

The efficacy of a single oral dose of a novel isoxazoline, sarolaner (Simparica™, Zoetis), for the treatment and control of flea infestations on dogs was confirmed in five laboratory studies. The studies were conducted using adult purpose-bred Beagles and/or mixed breed dogs. All animals were individually identified and housed, and were allocated randomly to treatment with either placebo or sarolaner (eight to 10 per group) based on pretreatment parasite counts. Three studies used cat flea (Ctenocephalides felis felis) strains recently isolated from the field from the US, EU, or Australia; in the fourth study a laboratory strain (KS1) with documented tolerance to a number of insecticides such as fipronil, imidacloprid, and permethrin was used. In the fifth study, dogs were infested with dog fleas, Ctenocephalides canis. Dogs were treated orally on Day 0 with a placebo or a sarolaner tablet providing a minimum dose of 2mg/kg. Dogs were infested with approximately 100 unfed, adult fleas prior to treatment and at weekly intervals post-treatment. Comb counts were conducted to determine the numbers of viable fleas at 24h after treatment and after each subsequent infestation. Efficacy against C. felis and C. canis was 99.8-100% from treatment through Day 35. In all five studies, elimination of existing infestations was achieved within 24h after dosing, with only a single live C. felis found on one dog on Day 1. Similarly, control of flea challenges was achieved within 24h after infestation throughout the 35day study periods, with only single live C. felis found on two dogs on Day 28 in one study, and on a single dog on Day 35 in another study. There were no adverse reactions to treatment with sarolaner. These studies confirmed that a single oral dose of sarolaner at 2mg/kg provided highly effective treatment of existing C. felis infestations and persistent control of C. felis on dogs for 35days after treatment. Efficacy equivalent to that seen with C. felis was confirmed against C. canis and a known insecticide-tolerant strain of C. felis.