Pharmacokinetics and Clinical Effects of a Single Oral Dose of Trazodone in the Domestic Goat (Capra Hircus) as a Model for Wild Ruminants

Prud'homme, Yasmeen; Ferrell, Shannon T.; Beaudry, Francis; Beauchamp, Guy; Nichols, Sylvain; Desmarchelier, Marion

doi:10.1638/2019-0242

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…This study also examined the impact of co-administration of oral gabapentin on trazodone plasma concentrations, degree of sedation and observable side effects as these drugs have been administered Trazodone was rapidly absorbed in this study when administered alone or with gabapentin, with T max values of around 10 min for both T and TG groups. Absorption was faster than noted in humans (T max 1.34 ± 0.84 h), horses (1.71 ± 0.42 h), and dogs (7.42 ± 4.51 h;Jay et al, 2013;Knych et al, 2018;Nilsen & Dale, 1992) but similar to what has been observed in goats (15 ± 5.4 min) and pigeons (Desmarchelier et al, 2019, Prud'homme et al, 2021 The T max is reflective of the rate of absorption of a drug; however, both C max and T max are influenced through experimental design by sampling schedules (Chen et al, 2001). In this study, the highest concentrations seen in groups T and TG were seen at the first sampling period (10 min).…”

Section: Discussionsupporting

confidence: 80%

Pharmacokinetic, sedative, and physiological effects of oral compounded formulations of trazodone alone or in combination with gabapentin in male cats

Tucker

Sánchez

Valverde

et al. 2023

Vet Pharm & Therapeutics

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Trazodone and gabapentin are common oral sedatives in cats, used alone or combined, but no pharmacokinetic studies exist for trazodone in this species. The objective of this study was to determine the pharmacokinetics of oral trazodone (T) alone, or in combination with gabapentin (G) in healthy cats. Cats (n = 6) were randomly allocated to receive T (3 mg/kg) intravenously (IV), T (5 mg/kg) orally (PO), or T (5 mg/kg) and G (10 mg/kg) PO with a 1‐week washout period between treatments. Heart rate, respiratory rate, indirect blood pressure, and level of sedation were assessed, and venous blood samples were collected serially over 24 h. Analysis of plasma trazodone concentration was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Oral T administration resulted in a bioavailability of 54.9(7–96)%, and 17.2(11–25)% when administered with G. Tmax 0.17 (0.17–0.5) and 0.17 (0.17–0.75) h; Cmax 1.67 ± 0.91 and 1.22 ± 0.54 μg/mL, AUC 5.23 (2.0–18.76) and 2.37 (1.17–7.80) h*μg/mL; T1/2 5.12 ± 2.56 and 4.71 ± 1.07 h; for T and TG, respectively. Sedation was significant when compared to baseline in all groups from 20 or 45 min to 8 h indicating some lag between peak plasma concentration and sedative effects. Physiological variables remained within normal limits. This study concludes that oral trazodone is rapidly absorbed in healthy cats. Addition of gabapentin did not result in more profound sedation, showing no clinical advantage of combining these drugs in this study population.

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Section: Discussionsupporting

confidence: 80%

Pharmacokinetic, sedative, and physiological effects of oral compounded formulations of trazodone alone or in combination with gabapentin in male cats

Tucker

Sánchez

Valverde

et al. 2023

Vet Pharm & Therapeutics

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“…Our findings are similar to studies in other species. In a recent study, use of PO trazodone in goats at 10 mg/kg resulted in a 49% decrease in movement as well as a 31% decrease in activity level 11 . In dogs, owners reported a substantial decrease in activity and acceptance of crate confinement after orthopedic surgery after receiving PO trazodone at 7‐10 mg/kg q8‐12h 12 .…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, use of PO trazodone in goats at 10 mg/kg resulted in a 49% decrease in movement as well as a 31% decrease in activity level. 11 In dogs, owners reported a substantial decrease in activity and acceptance of crate confinement after orthopedic surgery after receiving PO trazodone at 7-10 mg/kg q8-12h. 12 In both studies, no relevant adverse effects of the medication at these high doses were reported.…”

Section: Discussionmentioning

confidence: 99%

The effects of orally administered trazodone on ambulation and recumbency in healthy horses

Hobbs,

Luethy,

Davis

et al. 2023

Veterinary Internal Medicne

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BackgroundTrazodone, a serotonin receptor antagonist and reuptake inhibitor, might be a useful adjunctive treatment in the initial management of horses with acute laminitis if it minimizes ambulation or encourages recumbency.Objectives(1) Evaluate the effects of PO trazodone on ambulatory activity and recumbency in healthy horses; and (2) assess the pharmacokinetics of multiple PO doses of trazodone.Animals/MethodsIn a randomized cross‐over design, 8 healthy horses received placebo or trazodone at 2 doses (2.5 and 7.5 mg/kg) PO q12h for 48 hours with a 14‐day washout period between treatments. Forelimb step frequency was measured using a hoof‐mounted accelerometer and continuous video monitoring was used to detect recumbency. Groups were compared using repeated measures analysis of variance with Tukey's post hoc test. Trazodone and m‐chlorophenylpiperazine (m‐CPP) plasma concentrations were determined by ultra‐high performance liquid chromatography‐tandem mass spectrometry and pharmacokinetics were analyzed using noncompartmental methods.ResultsStep frequency was lower in horses receiving 7.5 mg/kg trazodone than in the control group (mean step reduction: 44% ± 11%). Steps‐area under the curve were significantly lower in the 7.5 mg/kg group (mean ± SD: 3375 ± 525 steps × hour) as compared to the 2.5 mg/kg group (mean ± SD: 5901 ± 2232; P = .02) and compared to control (mean ± SD: 6590 ± 1241; P = .001). No difference was found in the number of recumbent episodes (P = .92) or total duration of recumbency (P = .9). Trazodone and m‐CPP achieved steady‐state concentrations, with an accumulation ratio of 1.45 ± 0.2.Conclusions and Clinical ImportanceAlthough it did not affect recumbency, trazodone at 7.5 mg/kg q12h decreased step frequency by approximately 44%.

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Effects of a Single Oral Dose of Trazodone on Behavior and Serum Cortisol Levels in Blue Wildebeest (Connochaetes Taurinus)

Prud'homme

Ferrell²,

Haefele³

et al. 2023

Journal of Zoo and Wildlife Medicine

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Pharmacokinetics and Clinical Effects of a Single Oral Dose of Trazodone in the Domestic Goat (Capra Hircus) as a Model for Wild Ruminants

Cited by 3 publications

References 26 publications

Pharmacokinetic, sedative, and physiological effects of oral compounded formulations of trazodone alone or in combination with gabapentin in male cats

Pharmacokinetic, sedative, and physiological effects of oral compounded formulations of trazodone alone or in combination with gabapentin in male cats

The effects of orally administered trazodone on ambulation and recumbency in healthy horses

Effects of a Single Oral Dose of Trazodone on Behavior and Serum Cortisol Levels in Blue Wildebeest (Connochaetes Taurinus)

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