Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs

Klopmann, Thilo von; Rambeck, B.; Tipold, Andrea

doi:10.1111/j.1748-5827.2006.00290.x

Cited by 71 publications

(95 citation statements)

References 17 publications

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“…7 Alternative AEDs such as levetiracetam, zonisamide, and gabapentine are only effective to a limited degree in managing PB-and KBrresistant canine epilepsy. 8,9 Pharmacokinetic theory proposes increased drug metabolism or altered expression of drug targets or drug transporter proteins in the blood-brain barrier (BBB) as possible mechanisms in resistance to AEDs. 6,7 A prime candidate in this respect is the permeability-glycoprotein (P-gp), a transmembrane protein encoded by the ABCB1 gene, also called multidrug resistance 1 gene (MDR1).…”

mentioning

confidence: 99%

Polymorphisms in the ABCB1 Gene in Phenobarbital Responsive and Resistant Idiopathic Epileptic Border Collies

Alves

Hülsmeyer

Jaggy

et al. 2011

Veterinary Internal Medicne

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Background: Variation in the ABCB1 gene is believed to play a role in drug resistance in epilepsy. Hypothesis/Objectives: Variation in the ABCB1 gene encoding the permeability-glycoprotein could have an influence on phenobarbital (PB) resistance, which occurs with high frequency in idiopathic epileptic Border Collies (BCs).Animals: Two hundred and thirty-six client-owned BCs from Switzerland and Germany including 25 with idiopathic epilepsy, of which 13 were resistant to PB treatment.Methods: Prospective and retrospective case-control study. Data were collected retrospectively regarding disease status, antiepileptic drug (AED) therapy, and drug responsiveness. The frequency of a known mutation in the ABCB1 gene (4 base-pair deletion in the ABCB1 gene [c.296_299del]) was determined in all BCs. Additionally, the ABCB1 coding exons and flanking sequences were completely sequenced to search for additional variation in 41 BCs. Association analyses were performed in 2 case-control studies: idiopathic epileptic and control BCs and PB-responsive and resistant idiopathic epileptic BCs.Results: One of 236 BCs (0.4%) was heterozygous for the mutation in the ABCB1 gene (c.296_299del). A total of 23 variations were identified in the ABCB1 gene: 4 in exons and 19 in introns. The G-allele of the c.-6-180T 4 G variation in intron 1 was significantly more frequent in epileptic BCs resistant to PB treatment than in epileptic BCs responsive to PB treatment (P raw 5 .0025).Conclusions and Clinical Importance: A variation in intron 1 of the ABCB1 gene is associated with drug responsiveness in BCs. This might indicate that regulatory mutations affecting the expression level of ABCB1 could exist, which may influence the reaction of a dog to AEDs.

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confidence: 99%

Polymorphisms in the ABCB1 Gene in Phenobarbital Responsive and Resistant Idiopathic Epileptic Border Collies

Alves

Hülsmeyer

Jaggy

et al. 2011

Veterinary Internal Medicne

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“…Overall, the efficacy of zonisamide to decrease seizure frequency by ≥50% in 23 epileptic dogs with generalized seizures has been reported to be 58–80% when used as an adjunctive antiepileptic medication 49, 50. The 80% efficacy refers to the first 4 months of zonisamide treatment 50.…”

Section: When Should a Second Aed Be Started And Which Should Be Used?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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“…Zonisamide may also be useful as a third drug (von Klopmann and others 2007). The half-life is typically about 15 hours, but it is hepatically metabolised, so care needs to be taken when using it with phenobarbital.…”

Section: Which Add-on Drug Should Be Used?mentioning

confidence: 99%

Treatment and monitoring of epilepsy in dogs

Chandler¹

2011

In Practice

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Epilepsy is a brain disorder and is defined as the propensity to have recurrent seizures. It is the most common chronic neurological disorder seen in dogs. Most dogs that present with recurrent seizures have idiopathic epilepsy, which is thought to have a genetic basis and has no identifiable underlying cause when a full diagnostic work-up is undertaken. Symptomatic epilepsies, which arise secondary to brain diseases such as intracranial neoplastic lesions or central nervous system inflammatory disorders, are less common. By addressing some of the most frequently asked questions relating to the treatment of seizures, this article suggests some practical and effective strategies for managing and monitoring dogs with idiopathic epilepsy.

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Prospective study of zonisamide therapy for refractory idiopathic epilepsy in dogs

Abstract: In dogs with refractory epilepsy, zonisamide may have a beneficial effect on seizure control. In three responder dogs, seizure activity relapsed possibly because of an induction of tolerance. Limiting factors are the high costs.

Cited by 71 publications

References 17 publications

Polymorphisms in the ABCB1 Gene in Phenobarbital Responsive and Resistant Idiopathic Epileptic Border Collies

Polymorphisms in the ABCB1 Gene in Phenobarbital Responsive and Resistant Idiopathic Epileptic Border Collies

2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs

Treatment and monitoring of epilepsy in dogs

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