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Abstract

OBJECTIVE

To estimate the number of patients linked to vet-shopping behavior (the solicitation of controlled substance prescriptions from multiple veterinarians for misuse) in the United States using 2014–2019 data and characterize mandates for veterinarians to examine prescription drug monitoring programs (PDMPs) before prescribing controlled substances as of April 2021.

SAMPLE

National database reporting prescription dispensing from 92% of US pharmacies from 2014 through 2019.

PROCEDURES

The annual number of patients with dispensed prescriptions for opioid analgesics, opioid cough-and-cold medications, or benzodiazepines from ≥ 4 veterinarians was calculated. State veterinary medical associations were contacted for information on veterinarian PDMP use mandates.

RESULTS

From 2014 through 2019, the number of patients with prescriptions for any class of controlled substances from ≥ 4 veterinarians tripled from 935 to 2,875 (+207.5%). The number of patients with opioid cough-and-cold medication prescriptions from ≥ 4 veterinarians rose from 150 to 1,348 (+798.9%). The corresponding number for benzodiazepines rose from 185 to 440 (+137.8%). The corresponding number for opioid analgesics peaked at 868 in 2016 before decreasing to 733 in 2019. In April 2021, 10 states mandated veterinarians to examine PDMP records of owners or animals before prescribing controlled substances; 3 mandates excluded benzodiazepines.

CLINICAL RELEVANCE

Vet shopping in the US may be increasingly common. Mandates for veterinarians to examine PDMPs before prescribing controlled substances might facilitate detection of this behavior. However, benefits of mandates should be weighed against their potential burden on veterinarians.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To assess drug-drug interactions between cannabidiol (CBD) and phenobarbital (PB) when simultaneously administered to healthy dogs.

ANIMALS

9 healthy, purpose bred Beagles.

PROCEDURES

A 3-phase prospective, randomized pharmacokinetic (PK) interaction study of CBD and PB was performed as follows: phase 1, CBD PK determination and evaluation of CBD tolerability by 3 single-dose CBD (5 mg/kg, 10 mg/kg, and 20 mg/kg) protocols followed by 2-week CBD dosing; phase 2, a single-dose, 3-way, crossover PK study of CBD (10 mg/kg), PB (4 mg/kg), or CBD (10 mg/kg) administration plus PB (4 mg/kg); and phase 3, evaluation of chronic PB (4 mg/kg, q 30 d) administration followed by single-dose CBD (10 mg/kg) PK study.

RESULTS

Although there were variations in CBD PK variables in dogs receiving CBD alone or in conjunction with PB, significance differences in CBD PK variables were not found. No significant difference was observed in PB PK variables of dogs receiving PB alone or with CBD. During chronic CBD administration, mild gastrointestinal signs were observed in 5 dogs. At daily CBD doses of 10 to 20 mg/kg/d, hypoxia was observed in 5 dogs and increased serum alkaline phosphatase (ALP) activities (range, 301 to 978 U/L) was observed in 4 dogs. A significant increase in ALP activity was observed with chronic administration of CBD during phase 1 between day 0 and day 14.

CONCLUSIONS AND CLINICAL RELEVANCE

No significant PK interactions were found between CBD and PB. Dose escalation of CBD or adjustment of PB in dogs is not recommended on the basis of findings of this study.

Free access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To characterize the pharmacokinetics of mycophenolate mofetil (MMF) following single-dose IV or PO administration, characterize the pharmacokinetics of MMF following long-term PO administration, and describe the clinicopathologic effects of long-term MMF administration in horses.

ANIMALS

12 healthy adult horses.

PROCEDURES

In phase 1, 6 horses received a single IV (2.5 mg/kg) or PO (5 mg/kg) dose of MMF in a randomized balanced crossover assessment (≥ 2-week interval between administrations). In phase 2, 6 other horses received MMF for 60 days (5 mg/kg, PO, q 24 h for 30 days and then 5 mg/kg, PO, q 48 h for an additional 30 days).

RESULTS

Following IV (single-dose) or PO (single- or multiple-dose) administration, MMF was rapidly converted to mycophenolic acid. For single-dose PO administration, mean ± SD maximum plasma mycophenolic acid concentration was 1,778.3 ± 441.5 ng/mL at 0.71 ± 0.29 hours. For single-dose IV administration, mean systemic clearance and volume of distribution at steady state were 0.689 ± 0.194 L/h/kg and 1.57 ± 0.626 L/kg, respectively. Following single doses, mean terminal half-life was 3.99 ± 0.865 hours for IV administration and 4.02 ± 1.01 hours for PO administration. The accumulation index following long-term PO administration was 1.0 ± 0.002, and the terminal half-life was 4.59 ± 1.25 hours following the final dose on day 60. None of the horses developed abnormal clinical signs or had any consistently abnormal clinicopathologic findings.

CONCLUSIONS AND CLINICAL RELEVANCE

Further investigation of the clinical efficacy of long-term MMF treatment of horses with autoimmune diseases is warranted.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the safety and pharmacokinetics of various doses of plant-derived cannabidiol (CBD) versus placebo following repeated oral administration.

ANIMALS

20 healthy adult Beagles.

PROCEDURES

In a randomized, blinded, placebo-controlled trial, dogs were randomized to 5 groups balanced in body weight and sex (n = 4 dogs/group) and received a CBD (1, 2, 4, or 12 mg/kg; from cannabis extract) or placebo oil formulation PO once daily for 28 days. Outcome variables were assessed through daily health observations, veterinary examinations, CBC, and serum biochemical analysis. Blood samples were collected at various time points to estimate 24-hour pharmacokinetic profiles of CBD and selected metabolites (7-carboxy-CBD and 7-hydroxy-CBD).

RESULTS

Repeated CBD administration was well tolerated by dogs, with no clinically important changes in measured safety outcomes. Veterinary examinations revealed no clinically important abnormal findings. Adverse events were mild in severity. Relative to placebo administration, CBD administration at 12 mg/kg/d resulted in more gastrointestinal adverse events (mainly hypersalivation) and significantly higher serum alkaline phosphatase activity. Total systemic exposure to CBD increased on a dose-dependent basis following both acute (first dose) and chronic (28 days) administration. Within each CBD dose group, repeated administration increased total systemic exposure to CBD 1.6- to 3.3-fold. The 24-hour trough plasma CBD concentrations were also dose dependent, with a steady state reached following 2 weeks of administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Repeated, daily oral administration of the CBD formulation led to dose-dependent increases in total systemic exposure to CBD and 24-hour trough plasma concentrations in healthy dogs. These findings could help guide dose selection.

Full access
in American Journal of Veterinary Research