Pharmacokinetics, bioavailability, and hemodynamic effects of trazodone after intravenous and oral administration of a single dose to dogs

Jay, Ariane R.; Krotscheck, Ursula; Parsley, Elizabeth; Benson, Lisa; Kravitz, Ariel; Mulligan, Abby; Silva, Jharon; Mohammed, Hussni O.; Schwark, Wayne S.

doi:10.2460/ajvr.74.11.1450

Cited by 51 publications

(84 citation statements)

References 20 publications

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“…8 A pharmacokinetic study of single-dose oral trazodone in dogs revealed an elimination half-life of 166 ± 47 minutes. 13 In the present study, cases in which the duration of action seemed insufficient, on an individual basis the trazodone dose schedule was increased to three times daily.…”

Section: Discussionmentioning

confidence: 72%

“…A recent single dose pharmacokinetic study of trazodone in six dogs, found that when given orally, trazodone produced mild sedation with no observable side effects. 13 In anesthetized dogs, trazodone has been shown to have very little effect on cardiac function, compared with equally effective dosages of imipramine. 14 These characteristics make trazodone an ideal agent to decrease anxiety, agitation, and distress associated with confinement in post-surgical dogs.…”

Section: Introductionmentioning

confidence: 99%

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Use of trazodone to facilitate postsurgical confinement in dogs

Gruen¹,

Roe²,

Griffith³

et al. 2014

javma

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Objective To investigate the safety and efficacy of the oral serotonin antagonist/reuptake inhibitor trazodone hydrochloride to facilitate confinement and calming after orthopedic surgery in dogs. Design Prospective open-label trial. Animals 36 client-owned dogs. Procedures Healthy dogs were recruited when presented for pre-surgical evaluation for orthopedic procedures. Starting the day after surgery, dogs were administered trazodone (~3.5 mg/kg, per os (PO), q12h) with tramadol (4–6 mg/kg, PO, q8–12h) for pain management. After 3 days, tramadol was discontinued and trazodone was increased (~7 mg/kg, PO, q12h) and maintained for at least 4 weeks. If needed, trazodone dosage was increased to 7–10 mg/kg, PO, q8h. Clients completed electronic surveys rating their dogs’ confinement tolerance, calmness/hyperactivity level, and responses to specific provocative situations, prior to surgery and at 1, 2, 3, and 4 weeks and at the post-surgical evaluation (8–12 weeks). Results The majority of clients (~90%) reported that, when given trazodone during the 8–12 weeks following orthopedic surgery, their dogs improved moderately or extremely with regard to confinement tolerance and calmness. Trazodone was well tolerated, even in combination with non-steroidal drugs, antibiotics, and other medications; no dogs were withdrawn from the study due to adverse reactions. Client-reported median onset of action of trazodone was 31–45 minutes and median duration of action was four or more hours. Conclusions and Clinical Relevance The results suggest that oral trazodone is a safe and efficacious medication that may be used to facilitate confinement and enhance behavioral calmness of dogs during the critical recovery period following orthopedic surgery.

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Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Use of trazodone to facilitate postsurgical confinement in dogs

Gruen¹,

Roe²,

Griffith³

et al. 2014

javma

View full text Add to dashboard Cite

show abstract

“…The actual extent of absorption could not be determined due to the lack of an intravenous dose. Intravenous dosing was not performed due to the unacceptable level of adverse effects noted in dogs and horses, including tachycardia, aggression/excitation and whole body tremors (Jay et al., ; Knych et al., ). This, in addition to the lack of a commercially available injectable formulation, makes intravenous dosing unlikely to be clinically relevant.…”

Section: Discussionmentioning

confidence: 99%

“…A linear relationship existed between plasma concentrations and sedation and ataxia scores at the 10 mg/kg dose where oversedation was noted in three of six horses. Behavioural calming effects in dogs are seen at concentrations between 0.13 and 2 μg/ml (Jay et al., ). A threshold concentration of 0.7 μg/ml has been described for humans being treated for major depressive order (Mihara et al., ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics, pharmacodynamics and clinical use of trazodone and its active metabolite m‐chlorophenylpiperazine in the horse

Davis

Schirmer

Medlin

2018

Vet Pharm & Therapeutics

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Trazodone is a serotonin receptor antagonist and reuptake inhibitor used extensively as an anxiolytic in human and small animal veterinary medicine. The aims of this study were to determine the pharmacokinetics of oral trazodone in experimental horses and to evaluate the effect of oral trazodone in clinical horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg. Plasma concentrations of trazodone and its metabolite (m-CPP) were determined via UPLC-MS/MS. Noncompartmental pharmacokinetic analysis, sedation and ataxia scores were determined. Trazodone was rapidly absorbed after oral administration with a maximum concentration of 2.5-4.1 μg/ml and half-life of the terminal phase of approximately 7 hr. The metabolite was present at low levels in all horses, representing only 2.5% of the total area under the curve. In experimental horses, concentration-dependent sedation and ataxia were noted, lasting up to 12 hr. For clinical cases, medical records of horses treated with trazodone for various abnormal behaviours were reviewed and data were summarized. Trazodone was successful in modifying behavioural problems to some degree in 17 of 18 clinical cases. Tolerance and subsequent lack of drug effect occurred in two of 18 clinical cases following 14 or 21 days of use. In both populations of horses, adverse effects attributed to trazodone include oversedation, muscle fasciculations and transient arrhythmias.

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“…One study of trazodone in conscious dogs found six of six greyhounds developed a transient tachycardia following intravenous administration of 8 mg/kg trazodone and three of the six developed signs of aggression. An oral dose of 8 mg/kg had no such adverse effects (Jay and others 2013). However, no significant increases in heart rate (HR) were reported in pentobarbital-anaesthetised dogs receiving up to 30 mg/kg trazodone (Gomoll and others 1979).…”

Section: Discussionmentioning

confidence: 99%