Anticonvulsant activity and tolerance of ELB138 in dogs with epilepsy: a clinical pilot study.
ABSTRACT A new antiepileptic and anxiolytic drug, ELB138, was evaluated in a clinical pilot study in dogs with newly diagnosed or chronic idiopathic epilepsy. The purpose was to verify clinically the anticonvulsant effectiveness of this substance, which had already been demonstrated experimentally. Data from 29 dogs treated with ELB138 were compared with results obtained retrospectively from 82 dogs treated with conventional antiepileptic medication. The reduction in seizure frequency using ELB138 in dogs with newly diagnosed idiopathic epilepsy was comparable to the reduction in dogs treated either with phenobarbital or primidone. In dogs with chronic epilepsy and add-on therapy with either ELB138 or potassium bromide, such supplementation reduced the seizure frequency and the duration and severity of seizures. The most obvious difference between ELB138 treatment and conventional medications became clear in the evaluation of side effects, which in those dogs treated with ELB138 were rare, and consisted mostly of transient polyphagia. This pilot study confirmed that ELB138 has a potent anticonvulsant effect in dogs with idiopathic epilepsy. These results will form the basis for a multicentre, blinded study.
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ABSTRACT: The anticonvulsant activity and safety of imepitoin, a novel antiepileptic drug licensed in the European Union, were evaluated in a multicentre field efficacy study as well as in a safety study under laboratory conditions. Efficacy of imepitoin was compared with phenobarbital in 226 client-owned dogs in a blinded parallel group design. The administration of imepitoin twice daily in incremental doses of 10, 20 or 30 mg/kg demonstrated comparable efficacy to phenobarbital in controlling seizures in dogs. The frequency of adverse events including somnolence/sedation, polydipsia and increased appetite was significantly higher in the phenobarbital group. In phenobarbital-treated dogs, significantly increased levels of alkaline phosphatase, gamma-glutamyl-transferase and other liver enzymes occurred, while no such effect was observed in the imepitoin group. In a safety study under laboratory conditions, healthy beagle dogs were administered 0, 30, 90 or 150 mg/kg imepitoin twice daily for 26 weeks. A complete safety evaluation including histopathology was included in the study. A no-observed-adverse-event level of 90 mg/kg twice daily was determined. These results indicate that imepitoin is a potent and safe antiepileptic drug for dogs.Journal of Veterinary Pharmacology and Therapeutics 07/2014; · 1.32 Impact Factor
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ABSTRACT: Background Various antiepileptic drugs (AEDs) are used for the management of canine idiopathic epilepsy (IE). Information on their clinical efficacy remains limited. A systematic review was designed to evaluate existing evidence for the effectiveness of AEDs for presumptive canine IE. Electronic searches of PubMed and CAB Direct were carried out without date or language restrictions. Conference proceedings were also searched. Peer-reviewed full-length studies describing objectively the efficacy of AEDs in dogs with IE were included. Studies were allocated in two groups, i.e. blinded randomized clinical trials (bRCTs), non-blinded randomized clinical trials (nbRCTs) and non-randomized clinical trials (NRCTs) (group A) and uncontrolled clinical trials (UCTs) and case series (group B). Individual studies were evaluated based on the quality of evidence (study design, study group sizes, subject enrolment quality and overall risk of bias) and the outcome measures reported (in particular the proportion of dogs with ≥50% reduction in seizure frequency). Results Twenty-six studies, including two conference proceedings, reporting clinical outcomes of AEDs used for management of IE were identified. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. Only four bRCTs were identified in group A and were considered to offer higher quality of evidence among the studies. A good level of evidence supported the efficacy of oral phenobarbital and imepitoin and fair level of evidence supported the efficacy of oral potassium bromide and levetiracetam. For the remaining AEDs, favorable results were reported regarding their efficacy, but there was insufficient evidence to support their use due to lack of bRCTs. Conclusions Oral phenobarbital and imepitoin in particular, as well as potassium bromide and levetiracetam are likely to be effective for the treatment of IE. However, variations in baseline characteristics of the dogs involved, significant differences between study designs and several potential sources of bias preclude definitive recommendations. There is a need for greater numbers of adequately sized bRCTs evaluating the efficacy of AEDs for IE. Keywords: Systematic review; Epilepsy; Antiepileptic drugs; Treatment; CanineBMC Veterinary Research 10/2014; 10(257). · 1.74 Impact Factor
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ABSTRACT: Imepitoin is a novel anti-epileptic licensed in the European Union for the treatment of canine idiopathic epilepsy. The aim of this study was to characterize the pharmacokinetics of imepitoin in dogs and to evaluate the interaction with drug metabolizing enzymes. Upon administration of imepitoin tablets at a dose of 30 mg/kg to beagle dogs, high plasma levels were observed within 30 min following oral dosing, with maximal plasma concentrations of 14.9–17.2 μg/mL reached after 2–3 h. In a crossover study, co-administration of imepitoin tablets with food reduced the total AUC by 30%, but it did not result in significant changes in Tmax and Cmax, indicating lack of clinical relevance. No clinically relevant effects of sex and no accumulation or metabolic tolerance were observed upon twice daily dosing. Following single dose administration of 10–100 mg/kg, dose linearity was found. Administering [14C] imepitoin, high enteral absorption of 92% and primary fecal excretion were identified. Plasma protein binding was only 55%. At therapeutic plasma concentrations, imepitoin did not inhibit microsomal cytochrome P450 family liver enzymes in vitro. In rats, no relevant induction of liver enzymes was found. Therefore, protein binding or metabolism-derived drug–drug interactions are unlikely. Based on these data, imepitoin can be dosed twice daily, but the timing of tablet administration in relation to feeding should be kept consistent.Journal of Veterinary Pharmacology and Therapeutics 03/2014; · 1.35 Impact Factor