Disposition and safety of zonisamide after intravenous and oral single dose and oral multiple dosing in normal hound dogs

Boothe, Dawn M.; Perkins, Jeremy Dane

doi:10.1111/j.1365-2885.2008.00993.x

Cited by 39 publications

(60 citation statements)

References 43 publications

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“…Although ZNS is not FDA approved for use in dogs, it is now widely used as an anticonvulsant in this species . Limited information is available regarding safety, but small studies have suggested that routine clinical laboratory tests are unchanged with prolonged use, although serum thyroxine concentrations can be suppressed and mild hepatic changes might occur with sustained high doses (75mg/kg/day; approximately 5 times standard therapeutic doses) …”

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confidence: 99%

Renal Tubular Acidosis Associated with Zonisamide Therapy in a Dog

Cook

Allen

Espinosa

et al. 2011

Veterinary Internal Medicne

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A 5-year-old neutered male Schipperke was evaluated by the internal medicine service at Texas A&M College of Veterinary Medicine and Biomedical Sciences for mild increases in blood urea nitrogen (BUN) and creatinine concentrations. Parameters on an automated complete blood count a performed at the same time were within the reference ranges. The dog had a 3-year history of epileptiform seizures, which had been successfully managed for 18 months with oral zonisamide (ZNS) at a dosage of 7.9-8.4 mg/kg every 12 hours. Peak serum ZNS concentration had been measured 1 year earlier, and was within the target range at 39 lg/mL.On presentation to the internal medicine service, the dog was alert and responsive. Physical examination was essentially unremarkable, although the dog panted persistently and appeared agitated. A serum chemistry panel was performed b ; notable laboratory findings included hyperchloremia (124 mmol/L; normal: 107-116 mol/L), hypernatremia (150 mmol/L; normal: 139-147 mmol/L), hypokalemia (3.1 mmol/L; normal: 3.3-4.6 mmol/L), hypophosphatemia (1.6 mg/dL; normal: 2.9-6.2 mg/dL), and low total carbon dioxide (TCO 2 ; 11 mmol/L, reference range: 21-28 mmol/L). BUN and creatinine were 25 mg/dL (normal: 5-29 mg/dL) and 1.5 mg/dL (normal: 0.3-2.0 mg/dL), respectively. Urine, collected via cystocentesis, was adequately concentrated with a specific gravity of 1.039 c and a urine pH of 6.5 based on dipstick assessment.d Trace proteinuria was confirmed with a sulfosalicylic acid test. Urine protein:creatinine ratio was < 0.02 (< 0.5 considered normal). Urine culture produced a single colony of a Micrococcus species on the 1 : 1,000 dilution plate; this was assumed to be a contaminant. Ultrasonographic examination of the abdomen indicated hyperechogenicity of the inner part of each renal cortex; renal size was within normal limits bilaterally. The rest of the abdominal contents was unremarkable. Systolic blood pressure was measured indirectly using a Doppler device e and was within the reference range at 115-120 mmHg. Six hours after dosing, serum ZNS concentration was 38 lg/dL (target range: 10-40 lg/dL).The metabolic disturbance was characterized as a hyperchloremic, normal anion gap metabolic acidosis with a low sodium-chloride difference of 5.5 (normal: 27.1-32.2), normal total plasma concentration of nonvolatile weak buffers (Atot), and normal strong ion gap.

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confidence: 99%

Renal Tubular Acidosis Associated with Zonisamide Therapy in a Dog

Cook

Allen

Espinosa

et al. 2011

Veterinary Internal Medicne

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“…In a pharmacokinetic study of healthy dogs given zonisamide at 10.3 mg/kg PO q12h for 8 weeks, mean serum total T4 concentration decreased below the normal reference range but mean free serum T4 and TSH concentrations were within the reference range after 6 months of treatment. Increases in serum ALP activity and serum calcium concentration and decreases in serum total protein and albumin concentrations were reported compared to baseline but remained within reference range 61. A small but statistically significant decrease in serum albumin concentration and an increase in ALP activity have been reported in research dogs given zonisamide at a dosage of 75 mg/kg/day for 52 weeks 98.…”

Section: What Are the Risks Of Treatment?mentioning

confidence: 80%

“…Metabolic tolerance is present when progressive dose increases without concurrent parallel increase in serum drug concentration occurs, most likely because of other drugs that are p450 enzyme inducers or genetic variations. Conversely, phenobarbital will increase clearance of several other AEDs, including levetiracetam,59, 60 zonisamide61 and clorazepate 62…”

Section: How Should Monitoring Be Performed?mentioning

confidence: 99%

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs

Podell

Volk

Berendt

et al. 2016

Veterinary Internal Medicne

131

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This report represents a scientific and working clinical consensus statement on seizure management in dogs based on current literature and clinical expertise. The goal was to establish guidelines for a predetermined, concise, and logical sequential approach to chronic seizure management starting with seizure identification and diagnosis (not included in this report), reviewing decision‐making, treatment strategies, focusing on issues related to chronic antiepileptic drug treatment response and monitoring, and guidelines to enhance patient response and quality of life. Ultimately, we hope to provide a foundation for ongoing and future clinical epilepsy research in veterinary medicine.

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“…Thus, knowledge of how long it takes to achieve a steady‐state plasma concentration and whether or not there is dose‐dependency is necessary to determine an optimal dosage regimen for zonisamide. There is one previous study concerning the pharmacokinetics after single and multiple administrations of zonisamide in dogs (Boothe & Perkins, 2008). However, dose‐dependency and time to achieve a steady state at a range of clinical doses of zonisamide are still unclear.…”

Section: Trough Concentrations Of Zonisamide In Plasma Whole Bloodmentioning

confidence: 99%