Pharmacokinetic of two oral doses of a 1:20 THC:CBD cannabis herbal extract in cats.

Objective: To determine the pharmacokinetics (PK) of two oral doses of a Cannabis herbal extract (CHE) containing 1:20 THC:CBD in 12 healthy Domestic Shorthair cats. Methods: Single-dose PK were assessed after oral administration of CHE at low or high dose (2 mg CBD + 0.1 mg THC, or 5 mg CBD + 0.25 mg THC per kg bw, respectively; n = 6 per group) in fasting cats. Blood samples were drawn up to 48 h following CHE administration. Plasma samples were analyzed for CBD, THC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH using a previously validated LC-MS/MS method. Results: CBD and THC were quickly absorbed (mean Tmax of 2.4-2.9 h). Maximum plasma concentrations (Cmax) ranged from 36-511 ng/mL and 6.8-61 ng/mL for CBD and THC, respectively. Elimination was initially rapid for both CBD and THC, though a prolonged elimination phase was noted for CBD in some cats (T1/2 λ up to 26 h). Dose-adjusted Cmax and AUC0-last values were not statistically significantly different (p > 0.05) between dose groups indicating CBD and THC concentrations increased in a manner proportional (linear) to the dose. Dose-adjusted THC Cmax and AUC0-last were significantly higher than the corresponding dose-adjusted CBD parameters (p < 0.01). Low concentrations of the metabolite 6-OH-CBD were quantified but metabolites 7-OH-CBD, 11-OH-THC, and THC-COOH were not detected in any plasma samples. Inter-individual variance was notable. Salivation shortly after dosing was observed in two cats in the high dose group; these animals had substantially lower cannabinoid concentrations than other cats in this group. No adverse clinical signs (including vomiting, change in mentation or other neurological signs) were noted. Clinical significance: Although cats did not display adverse effects after administration of a single oral dose of 1:20 THC:CBD CHE formulation at 2 or 5 mg CBD/kg bw, observed plasma concentrations were highly variable but generally lower than in dogs receiving the same dose and formulation. Administration of CHE in the fasting state may not optimize CBD absorption, and oral dosing may be challenging when administering an oil-based CHE in some cats.

An Internet survey of risk factors for injury in North American dogs competing in flyball.

A survey was used to investigate injuries in dogs competing in flyball. Complete surveys were obtained from 272 respondents with 589 dogs. In the past year, 23.3% of dogs were injured, with 34.1% injured during their career to date. Common injury sites were paws/digits, back, shoulder, and iliopsoas muscle/groin. Injury in previous years, modified by weight:height ratio, was a significant risk factor for injury. Dogs > 2 y of age had increased risk of injury, as did dogs with best times < 4.0 s. Canadian dogs had increased risk of injury (30.7% injured) compared to United States dogs (20.1% injured). This relationship was modified by participation in other sports, which generally reduced risk of injury in Canadian dogs. Further investigation of risk factors should include differences in training and competition between the United States and Canada, as well as injury prevention strategies.

Un sondage Internet sur les facteurs de risque de blessure chez les chiens nord-américains participant au flyball. Un sondage a été utilisé pour enquêter sur les blessures chez les chiens participant au flyball. Des enquêtes complètes ont été obtenues auprès de 272 répondants avec 589 chiens. Au cours de la dernière année, 23,3 % des chiens ont été blessés, et 34,1 % au cours de leur carrière à ce jour. Les sites de blessure les plus courants étaient les pattes/doigts, le dos, l'épaule et l'aine/muscle psoas iliaque. Les blessures des années précédentes, modifiées par le rapport poids/taille, étaient un facteur de risque important de blessures. Les chiens de plus de 2 ans présentaient un risque accru de blessures, tout comme les chiens avec les meilleurs temps < 4,0 s. Les chiens canadiens présentaient un risque accru de blessures (30,7 % de blessés) par rapport aux chiens américains (20,1 % de blessés). Cette relation était modifiée par la participation à d'autres sports, ce qui réduisait généralement le risque de blessure chez les chiens canadiens. Une enquête plus approfondie sur les facteurs de risque devrait inclure les différences d'entraînement et de compétition entre les États-Unis et le Canada, ainsi que des stratégies de prévention des blessures.(Traduit par Dr Serge Messier).

Pharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBD Cannabis Herbal Extract in Dogs.

Objective: To determine the pharmacokinetics (PK) and safety of various oral doses of a Cannabis herbal extract (CHE) containing a 1:20 ratio of Δ9-tetrahydrocannabinol (THC):cannabidiol (CBD) in 13 healthy Beagle-cross dogs. Methods: Single-dose PK was assessed after oral administration of CHE at low, medium, or high doses [2, 5, or 10 mg CBD and 0.1, 0.25, or 0.5 mg THC per kg of body weight (bw), respectively; n = 6 per group]. Dogs were monitored for adverse events for up to 48 h post-dose. Evaluations of neurological signs, clinical laboratory abnormalities, and other adverse events were performed in two separate study phases: a multiple-dose phase with 12 dogs receiving five medium doses (5 mg CBD/kg bw) at 12 h intervals, and a single low-dose (2 mg CBD/kg bw), randomized, blinded, negative controlled study with 13 dogs. Results: Cannabinoids CBD, THC, CBC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH were quantified in plasma. CBD and THC were rapidly absorbed (mean T max of 1.9-2.3 h) and initially depleted rapidly (mean CBD T 1/2ß of 2.3-2.6 h). A prolonged elimination phase (mean CBD T 1/2λ of 13.3-24.4 h) was observed. CBD and THC concentrations increased in a dose-dependent (non-linear) manner, with disproportionally greater cannabinoid exposure relative to the dose increase. Neurological signs (hyperesthesia or proprioceptive deficits) were noted in five of six dogs in the high-dose group, but only occasionally or rarely in the medium- and low-dose groups, respectively. Presence and severity of clinical signs correlated with plasma cannabinoid concentrations. Dogs appeared to develop a tolerance to cannabinoid effects after multiple CHE doses, with fewer neurological signs noted after the final (fifth) vs. first dose. No clinically meaningful changes in blood count or chemistry values occurred after multiple CHE doses. Clinical Significance: Dogs tolerated the 1:20 THC:CBD formulation well at low and medium doses, but clinically meaningful neurological signs were observed at high doses. Because of non-proportional increases in plasma cannabinoid concentrations with increasing doses, as well as potential differences in CHE product composition and bioavailability, the possibility of adverse events and dose regimen consistency should be discussed with dog owners.

Assessment of veterinary drug residues in food: Considerations when dealing with sub-optimal data.

The use of veterinary drugs in food-producing animals may lead to residues in animal-derived foodstuffs, potentially posing a risk to human safety. While the process of veterinary drug residue risk assessment continues to evolve as new data emerges, a recurring challenge is when sub-optimal or incomplete data are provided with the expectation of supporting a robust risk assessment. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) is comprised of international experts who routinely deal with such data challenges when performing veterinary drug residue evaluations. Recent developments in veterinary drug residue risk assessment are described, including specific consequences of sub-optimal data during the risk assessment process. When feasible, practical solutions to such challenges are also highlighted. Case examples from recent JECFA veterinary drug evaluations are provided to clearly quantify and illustrate the concepts described. The information provided is intended to facilitate the generation of improved quality data, enabling more timely and robust veterinary drug residue risk assessments.

Characterizing chronic and acute health risks of residues of veterinary drugs in food: latest methodological developments by the joint FAO/WHO expert committee on food additives.

The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA's considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.

A survey of antimicrobial use during bovine abdominal surgery by western Canadian veterinarians.

Members of the Western Canadian Association of Bovine Practitioners were surveyed regarding their use of antimicrobials in bovine abdominal surgery. Perioperative antimicrobials were used in 100% of abdominal surgeries by 96 of 98 respondents. Although postoperative administration was the most common perioperative period for antimicrobial use, intraoperative intraperitoneal use was reported by more than half of the veterinarians surveyed. Procaine penicillin G and oxytetracycline were the most commonly administered perioperative antimicrobials.

Ivermectin use and resulting milk residues on 4 Canadian dairy herds.

The Canadian gFARAD was contacted for milk withdrawal recommendations after multiple cases of topical ivermectin use in lactating dairy cows. The following 4 cases included pertinent milk residue information and illustrate the challenges faced by producers, veterinarians, and regulatory authorities when ivermectin use occurs in dairy cows.