背景:影响犬血清左乙拉西坦浓度的因素未知,可能会影响左乙拉西坦控制癫痫犬癫痫发作的功效。
目的:狗需要更高的PO剂量的左乙拉西坦以达到对人类有效的血清浓度。确定可能影响血清左乙拉西坦浓度的因素,并证明某些癫痫犬的剂量调整。
方法:69只患者自养的癫痫犬,单独或联合使用左乙拉西坦治疗,基于左乙拉西坦的127谷血清浓度测量。
方法:回顾性队列研究。线性混合模型用于评估患者信号和同时给药对左乙拉西坦血清浓度的影响以及左乙拉西坦血清浓度对癫痫发作频率降低的影响。
结果:左乙拉西坦的PO剂量显着解释了血清左乙拉西坦浓度的变化,单药治疗的因果关系更强(R2=0.59,P<.001)。苯巴比妥以剂量依赖性方式显著降低血清左乙拉西坦浓度(R2=0.30,P=.003)。根据我们的模型,当单独使用或与7mg/kg/天的苯巴比妥同时使用时,需要99-216mg/kg/天的左乙拉西坦剂量才能获得20μg/mL的血清左乙拉西坦浓度。没有发现其他因素影响血清左乙拉西坦浓度。无法确定治疗范围。
结论:我们的数据表明,左乙拉西坦需要99-216mg/kg/天的剂量才能达到已知对人体有效的血清浓度,尤其是与苯巴比妥同时给药时。
BACKGROUND: Factors affecting serum concentrations of levetiracetam in dogs are unknown and could affect the efficacy of levetiracetam in controlling seizures in dogs with epilepsy.
OBJECTIVE: Higher PO doses of levetiracetam will be needed in dogs to achieve serum concentrations shown to be effective in humans. Determine factors that could influence serum levetiracetam concentrations and justify dose adjustment in some epileptic dogs.
METHODS: Sixty-nine client-owned dogs with epilepsy treated with levetiracetam alone or in combination, based on 127 trough serum concentration measurements of levetiracetam.
METHODS: Retrospective cohort study. Linear mixed models were used to assess the effect of patient signalment and concurrent drug administration on serum concentrations of levetiracetam and the effect of serum concentration of levetiracetam on seizure frequency reduction.
RESULTS: The PO dose of levetiracetam significantly explained changes in serum levetiracetam concentration, and this causal link was stronger with monotherapy (R2 = 0.59, P < .001). Phenobarbital significantly decreased serum levetiracetam concentration in a dose dependent manner (R2 = 0.30, P = .003). Based on our model, a levetiracetam dosage of 99-216 mg/kg/day is necessary to obtain a serum levetiracetam concentration of 20 μg/mL when used alone or concurrently with 7 mg/kg/day of phenobarbital. No other factors were found to influence serum levetiracetam concentrations. No therapeutic range could be identified.
CONCLUSIONS: Our data suggest that a dosage of 99-216 mg/kg/day of levetiracetam is needed to achieve a serum concentration known to be therapeutically effective in humans, especially when administered concomitantly with phenobarbital.