Steady-state pharmacokinetics of zonisamide in plasma, whole blood, and erythrocytes in dogs

Fukunaga, Koya; Saito, Miyoko; Muto, Makoto; Yoshioka, Ryosaku; Mishima, Kenichi; Fujiwara, Michihiro; Orito, Kensuke

doi:10.1111/j.1365-2885.2009.01097.x

Cited by 7 publications

(8 citation statements)

References 17 publications

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“…Other research demonstrated that ZNS reached a steady state within 4 days after repeated oral administrations (5, 10, 15, 30 mg/kg) of this agent and also showed that the canine dose-C min (minimal concentration) relationship, after repeated p.o. administration, exhibited linearity at 5-30 mg/kg (Fukunaga et al 2009).…”

Section: Zonisamidementioning

confidence: 88%

Characteristics of selected second-generation antiepileptic drugs used in dogs

Ziółkowski

Jaroszewski²,

Ziółkowska³

et al. 2012

Polish Journal of Veterinary Sciences

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A significant number of cases of clinical canine epilepsy remain difficult to control in spite of the applied treatment. At the same time, the range of antiepileptic drugs is increasingly wide, which allows efficient treatment. In the present paper we describe the pharmacodynamics and pharmacokinetics of the newer antiepileptic drugs which were licensed after 1990 but are still not widely used in veterinary medicine. The pharmacokinetic profiles of six of these drugs were tested on dogs. The results of experimental studies suggest that second generation antiepileptic drugs may be applied in mono- as well as in poli- treatment of canine epilepsy because of the larger safety margin and more advantageous pharmacokinetic parameters. Knowledge of the drugs’ pharmacokinetics allows its proper clinical appliance, which, in turn, gives the chance to improve the efficiency of pharmacotherapy of canine epilepsy.

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Section: Zonisamidementioning

confidence: 88%

Characteristics of selected second-generation antiepileptic drugs used in dogs

Ziółkowski

Jaroszewski²,

Ziółkowska³

et al. 2012

Polish Journal of Veterinary Sciences

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“…During Phase 2 of the study, there was a linear correlation between AUC and dose and C max and dose for the four doses studied in chickens. Linear pharmacokinetics of ZNS has been reported in humans and in dogs with repeated dosing, except when higher doses are administered (Fukunaga et al., 2010; Hashimoto et al., 1994; Peters & Sorkin, 1993; Walker et al., 1988). Saturation of the metabolic enzymes is often proposed as a cause of non‐linear pharmacokinetics of ZNS in mammals when higher doses are administered.…”

Section: Discussionmentioning

confidence: 99%

“…During the dose escalation, diarrhoea incidence and severity increased with increase in dose, with a correlation between severity of diarrhoea and weight loss reported. Although diarrhoea is not reported as a common side effect of ZNS in humans (Seino & Ito, 1997) and dogs (Boothe & Perkins, 2008; Dewey et al., 2004; Fukunaga et al., 2010), 50% of cats in a multiple dosing pharmacokinetic study developed diarrhoea (between other gastrointestinal signs such as anorexia and vomiting), without significant changes in body weight (Hasegawa et al., 2008). Because the concentration of the prepared ZNS solution remained at 10 mg/ml throughout Phase 2 of the study, birds were receiving close to 20 ml of the syrup‐based solution every 12 hr at the 80 mg/kg cohort.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of zonisamide after oral single dosing and multiple‐dose escalation administration in domestic chickens (Gallus gallus)

Matos

Noonan

Schaefer

et al. 2021

Veterinary Medicine & Sci

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Background There are few effective drugs for treatment of seizures in avian species. Objectives To investigate the pharmacokinetics and safety of zonisamide in chickens. Methods Phase 1: chickens (n = 4) received a single oral dose of zonisamide at 20 mg/kg. Blood samples were collected intermittently for 36 hr after dosing. Phase 2: chickens (n = 8) received zonisamide in a dose escalation protocol (20, 30, 60 and 80 mg/kg orally every 12 hr). The dose was increased weekly, and peak and trough blood samples were collected on Days 1, 3, and 7 each week. Two birds were randomly euthanized at the end of each week. Plasma zonisamide concentrations were analysed using a commercial immunoassay. Drug concentration vs. time data were subjected to non‐compartmental pharmacokinetic analysis. Results For Phase 1, peak plasma zonisamide (Cmax) was 15 ± 3 µg/ml at 2 ± 1 hr (Tmax). The disappearance half‐life was 6.5 ± 1 hr. Mean plasma concentrations remained within the (human) therapeutic range (10–40 µg/ml) for 6 hr. For Phase 2 of the study, plasma concentrations of zonisamide remained within or close to the recommended mammalian therapeutic range for birds in the 20 and 30 mg/kg dose. Area under the curve (AUC) and Cmax were dose dependent. Two birds developed immune‐mediated haemolytic anaemia. Conclusions Zonisamide appears to be a viable drug for use in chickens at a dose of 20 mg/kg orally every 12 hr.

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“…Zonisamide is a 1,2‐benzisoxazole‐3‐methanesulfonamide antiepileptic drug used in veterinary and human medicine (Dewey et al., 2004 ; Fukunaga et al., 2009 ; Schwartz et al., 2011 ). It is a benzisoxazole sulphonamide derivative, which unlike other common sulphonamide‐based drugs, lacks a non‐arylamine sulphonamide group.…”

Section: Introductionmentioning

confidence: 99%

“…It is a benzisoxazole sulphonamide derivative, which unlike other common sulphonamide‐based drugs, lacks a non‐arylamine sulphonamide group. The significance of the differing sulphonamide component in zonisamide and its role in adverse effects remains unknown (Fukunaga et al., 2009 ; Kanazono et al., 2021 ). Zonisamide is available in injectable and oral formulations with therapeutic dosages in dogs ranging from 5 to 15 mg/kg every 12 h (Brewer et al., 2014 ; Fukunaga et al., 2009 ; Kanazono et al., 2021 ; Podell et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Immune‐mediated polyarthritis and anterior uveitis secondary to zonisamide administration in a dog with refractory epilepsy

Baya,

Press,

Istvan

et al. 2024

Veterinary Medicine & Sci

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The objective of this article is to describe a case of suspected zonisamide‐induced immune‐mediated polyarthritis (IMPA) and anterior uveitis in a dog. A 7‐year‐old male neutered Siberian Husky with a history of refractory idiopathic epilepsy was presented for cluster seizures. Following the addition of zonisamide to the antiepileptic regime, the dog developed new IMPA and anterior uveitis. Within a few weeks of discontinuation of the zonisamide, the dog's IMPA and anterior uveitis resolved. These immune‐mediated conditions were thus presumed to be an idiosyncratic reaction to zonisamide. To our knowledge, this is the first report of IMPA and anterior uveitis in dogs associated with zonisamide administration at its recommended dose.

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Steady-state pharmacokinetics of zonisamide in plasma, whole blood, and erythrocytes in dogs

Cited by 7 publications

References 17 publications

Characteristics of selected second-generation antiepileptic drugs used in dogs

Characteristics of selected second-generation antiepileptic drugs used in dogs

Pharmacokinetics of zonisamide after oral single dosing and multiple‐dose escalation administration in domestic chickens (Gallus gallus)

Immune‐mediated polyarthritis and anterior uveitis secondary to zonisamide administration in a dog with refractory epilepsy

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