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Abstract

OBJECTIVE

To investigate the effects and duration of orally administered prednisolone on renal function evaluated by glomerular filtration rate (GFR) determination and creatinine (Cr) and symmetric dimethylarginine (SDMA) concentrations as well as on urinalysis, electrolytes, and hydric status in healthy dogs.

ANIMALS

14 healthy Beagles.

PROCEDURES

In this prospective double-masked placebo-controlled study, dogs were randomized after baseline evaluation to receive a 7-day course of either prednisolone (1.5 to 2.0 mg/kg, PO, q 12 h) or a placebo. A repeated-measure design was performed, each dog participating in 4 successive sampling sessions. Clinical data, systolic blood pressure, CBC, and biochemical analyses including serum SDMA concentration, GFR determination, urine output quantification, and complete urinalysis were performed for all dogs the day before (D0) and at the end of steroid administration (D7) as well as 2 weeks (D21) and 4 weeks (D35) after the end of treatment.

RESULTS

At D7, when compared with baseline, GFR increased significantly in treated dogs, whereas creatinine and SDMA concentrations decreased significantly. GFR and Cr but not SDMA modifications persisted significantly at D21. None of the variables differed significantly from baseline at D35. The OR of presenting an albumin band on urine electrophoresis was 2.4 times as high in treated versus control dogs (OR, 36; 95% CI, 1.8 to 719.4; P = 0.02).

CLINICAL RELEVANCE

A short-term course of immune-suppressive prednisolone treatment in healthy dogs leads to a sustained but reversible renal hyperfiltration state. Modification in electrolytic variables can affect the clinical interpretation of blood work in such patients.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine whether IV regional limb perfusion (IVRLP) performed in the cephalic vein with a wide rubber tourniquet (WRT) applied proximal and distal to the carpus results in a higher peak concentration (Cmax) of amikacin in the radiocarpal joint (RCJ), compared with the Cmax for IVRLP using a single WRT proximal to the carpus.

Animals

7 healthy adult horses.

Procedures

Horses underwent IVRLP using standing sedation with 2 g of amikacin sulfate diluted to 60 mL by use of saline (0.9% NaCl) solution in the cephalic vein with 2 different tourniquet techniques; proximal WRT (P) and proximal and distal WRT (PD). Synovial fluid was collected from the RCJ at 5, 10, 15, 20, 25, and 30 minutes after IVRLP. Tourniquets were removed after the 30-minute sample was collected. Blood samples from the jugular vein were collected at 5, 10, 15, 20, 25, 29, and 31 minutes after IVRLP. Amikacin concentration was quantified by a fluorescence polarization immunoassay. Median peak concentration (Cmax) of amikacin and time to maximum drug concentration (Tmax) within the RCJ were determined.

Results

Median peak concentration in the RCJ was 1331.4 μg/mL with technique P and 683.1 μg/mL with technique PD. Median Tmax occurred at 30 minutes with technique P and 25 minutes with technique PD. No significant (Cmax, P = 0.18; Tmax, P = 0.6) difference in amikacin Cmax or Tmax between techniques was detected.

Clinical Relevance

Placement of 2 WRTs offers no advantage to a single proximal WRT when performing IVRLP to deliver maximal amikacin concentrations to the RCJ using IVRLP.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine the pharmacokinetics and potential adverse effects of pimobendan after oral administration in New Zealand White rabbits (Ocytolagus cuniculi).

ANIMALS

10 adult sexually intact (5 males and 5 females) rabbits.

PROCEDURES

2 pilot studies were performed with a pimobendan suspension or oral tablets. Eight rabbits received 7.5 mg of pimobendan (mean 2.08 mg/kg) suspended in a critical care feeding formula. Plasma concentrations of pimobendan and O-demethylpimobendan (ODMP) were measured, and pharmacokinetic parameters were calculated for pimobendan by noncompartmental analysis. Body weight, food and water consumption, mentation, urine, and fecal output were monitored.

RESULTS

Mean ± SD maximum concentration following pimobendan administration was 15.7 ± 7.54 ng/mL and was detected at 2.79 ± 1.25 hours. The half-life was 3.54 ± 1.32 hours. Plasma concentrations of pimobendan were detectable for up to 24 hours. The active metabolite, ODMP, was detected in rabbits for 24 to 36 hours. An adverse event occurred following administration of pimobendan in tablet form in 1 pilot study, resulting in death secondary to aspiration. No other adverse events occurred.

CLINICAL RELEVANCE

Plasma concentrations of pimobendan were lower than previously reported for dogs and cats, despite administration of higher doses, and had longer time to maximum concentration and half-life. Based on this study, 2 mg/kg of pimobendan in a critical care feeding formulation should maintain above a target plasma concentration for 12 to 24 hours. However, further studies evaluating multiple-dose administration as well as pharmacodynamic studies and clinical trials in rabbits with congestive heart failure are needed to determine accurate dose and frequency recommendations.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons.

ANIMALS

8 healthy adult bearded dragons.

PROCEDURES

4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography.

RESULTS

The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours.

CLINICAL RELEVANCE

Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.

Restricted access
in American Journal of Veterinary Research

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 evaluate the effects of housing environment on oral absorption of acetaminophen in dogs.

ANIMALS

6 healthy Beagles.

PROCEDURES

Acetaminophen (325 mg, PO; mean dose, 31.1 mg/kg) was administered in a crossover study design with dogs housed in their normal environment or in a cage in an unfamiliar environment. There was a 7-day washout period between phases. Blood samples were collected for 24 hours following acetaminophen administration, and plasma acetaminophen concentrations were determined with high-pressure liquid chromatography.

RESULTS

A 2-compartment model with lag time was the best fit for both phases of the study. None of the primary or secondary pharmacokinetic parameters were significantly different between the 2 housing environments.

CLINICAL RELEVANCE

Findings suggested that in dogs, housing environment (normal environment vs a cage in an unfamiliar environment) did not significantly affect oral absorption and, by extension, gastric emptying of acetaminophen.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To identify an oral dose of grapiprant for red-tailed hawks (RTHAs; Buteo jamaicensis) that would achieve a plasma concentration > 164 ng/mL, which is considered therapeutic for dogs with osteoarthritis.

ANIMALS

6 healthy adult RTHAs.

PROCEDURES

A preliminary study, in which grapiprant (4 mg/kg [n = 2], 11 mg/kg [2], or 45 mg/kg [2]) was delivered into the crop of RTHAs from which food had been withheld for 24 hours, was performed to obtained pharmacokinetic data for use with modeling software to simulate results for grapiprant doses of 20, 25, 30, 35, and 40 mg/kg. Simulation results directed our selection of the grapiprant dose administered to the RTHAs in a single-dose study. Plasma grapiprant concentration, body weight, and gastrointestinal signs of RTHAs were monitored.

RESULTS

On the basis of results from the preliminary study and simulations, a grapiprant dose of 30 mg/kg was used in the single-dose study. The geometric mean maximum observed plasma concentration of grapiprant was 3,184 ng/mL, time to maximum plasma grapiprant concentration was 2.0 hours, and the harmonic mean terminal half-life was 17.1 hours. No substantial adverse effects were observed.

CONCLUSIONS AND CLINICAL RELEVANCE

Although the single dose of grapiprant (30 mg/kg) delivered into the crop achieved plasma concentrations > 164 ng/mL in the RTHAs, it was unknown whether this concentration would be therapeutic for birds. Further research that incorporates multidose assessments, safety monitoring, and pharmacodynamic data collection is warranted on the use of grapiprant in RTHAs from which food was withheld versus not withheld.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine plasma tramadol concentrations in cats following a single dose of oral and transdermal formulations and the pharmacokinetics for and the concentration of tramadol in the transdermal formulation.

ANIMALS

8 healthy client-owned domestic shorthair cats.

PROCEDURES

1 cat was orally administered 1 dose of tramadol (2 mg/kg), and 7 cats received 1 dose of a proprietary compounded tramadol gel product (median actual dose, 2.8 mg/kg) applied to their inner pinnae. Plasma tramadol concentrations were measured with high-performance liquid chromatography–mass spectrometry at fixed times over 24 hours.

RESULTS

Plasma tramadol concentrations were undetectable or much lower (range, < 1 to 4.3 ng/mL) following application of the transdermal formulation, compared with those following oral administration (maximum plasma tramadol concentration, 261.3 ng/mL [at 4 hours]). Tramadol pharmacokinetics for the transdermal formulation could not be determined. Tramadol concentrations of the transdermal gel product exceeded the estimated label dose in all analyzed gel samples, with concentrations greater than the 90% to 110% United States Pharmacopeia standard for compounded drugs.

CONCLUSIONS AND CLINICAL RELEVANCE

Application of 1 dose of the proprietary transdermal formulation did not yield clinically relevant plasma tramadol concentrations in cats. Although this proprietary formulation is currently available to prescribing veterinarians, it should be used with caution.

Restricted access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine an optimal ceftazidime dosing strategy in Northern leopard frogs (Lithobates pipiens) by evaluation of 2 different doses administered SC and 1 dose administered transcutaneously.

ANIMALS

44 Northern leopard frogs (including 10 that were replaced).

PROCEDURES

Ceftazidime was administered to frogs SC in a forelimb at 20 mg/kg (n = 10; SC20 group) and 40 mg/kg (10; SC40 group) or transcutaneously on the cranial dorsum at 20 mg/kg (10; TC20 group). Two frogs in each ceftazidime group were euthanized 12, 24, 48, 72, and 96 hours after drug administration. Plasma, renal, and skin concentrations of ceftazidime were measured by means of reversed-phase high-performance liquid chromatography. Four control frogs were used for assay validation.

RESULTS

Mean plasma half-life of ceftazidime in the SC20, SC40, and TC20 groups was 9.01 hours, 14.49 hours, and too low to determine, respectively. Mean maximum plasma ceftazidime concentration was 92.9, 96.0, and 1.3 μg/mL, respectively. For 24 hours after drug administration in the SC20 and SC40 groups, plasma ceftazidime concentration exceeded 8 μg/mL. Renal and skin concentrations were detectable at both doses and routes of administration; however, skin concentrations were significantly lower than renal and plasma concentrations.

CONCLUSIONS AND CLINICAL RELEVANCE

Findings indicated that ceftazidime administration to Northern leopard frogs at 20 mg/kg, SC, every 24 hours would achieve a plasma concentration exceeding the value considered effective against common amphibian pathogens. Transcutaneous administration of the injectable ceftazidime formulation at 20 mg/kg warrants further investigation but is not currently recommended because of a potential lack of efficacy.

Restricted access
in American Journal of Veterinary Research