Inhibitory effect of oxcarbazepine on high-frequency firing in peripheral nerve fibers

We assessed the effects of oxcarbazepine, an antiepileptic derivative of carbamazepine, on discharges in single cutaneous afferent fibers produced by repetitive high-frequency stimulation (mimicking the abnormal excitation of peripheral nerves in neuropathic pain and paresthesia). After intravenous administration of oxcarbazepine, the later responses in the train dropped out without the earlier ones being affected and, thus, the total number of spikes decreased. The latency of the responses to an individual pulse was unchanged. These results, which indicate that oxcarbazepine inhibits the generation of high-frequency firing without affecting impulse conduction, suggest that this drug may be useful against neuropathic pain and paresthesia.     

Caffeine reverses antinociception by oxcarbazepine by inhibition of adenosine A1 receptors: Insights using knockout mice

Oxcarbazepine is an anticonvulsant drug that has been explored as a novel therapeutic agent to treat neuropathic pain in humans. It produces antinociception in several preclinical models of pain, and these actions are blocked by methylxanthine adenosine receptor antagonists which implicates adenosine it its actions. In this study, the antinociceptive effect of oxcarbazepine, and the ability of caffeine to reverse its actions, were examined using the formalin test (2%) in wild-type mice and in mice lacking adenosine A₁ receptors by way of further exploring the involvement of adenosine in its actions. Oxcarbazepine produced dose-related suppression of formalin-evoked flinching responses in wild-type mice following both systemic and intraplantar administration, and this action was reversed by systemic and intraplantar administration of caffeine, respectively. The ability of oxcarbazepine to inhibit flinching after systemic and intraplantar administration was unaltered in homozygous (−/−) and heterozygous (+/−) adenosine A₁ receptor knockout mice. However, caffeine no longer reversed this antinociception. Our results indicate that, while adenosine A₁ receptors are not required for oxcarbazepine to produce antinociception in knockout mice, such receptors are essential in order to see caffeine reversal of this antinociceptive effect.     

奥卡西平合用喹硫平治疗老年期躁狂发作的随机开放试验

目的：评价奥卡西平合用喹硫平治疗老年期躁狂发作的疗效和安全性。方法：将60例老年期躁狂发作患者随机分为奥卡西平组和丙戊酸钠组各30例,分别给予奥卡西平0.6~1.2 g/d合并喹硫平0.2~0.6 g/d和丙戊酸钠0.6~1.2 g/d合并喹硫平0.2~0.6 g/d治疗4周。以Bech-Rafaelsen躁狂量表（BRMS）、临床总体疗效评定量表（CGI）以及药物副反应量表（TESS）评定疗效及不良反应。结果：两组治疗后BRMS、CGI评分均较治疗前显著下降（P<0.05）,TESS两组间差异比较无统计学意义（P>0.05）;两组不良反应均较少。结论：奥卡西平治疗老年期躁狂发作疗效确定,安全性良好。     

卡马西平与奥卡西平用于原发性三叉神经痛的疗效与不良反应比较

目的 比较卡马西平与奥卡西平治疗原发性三叉神经痛患者的疗效与不良反应.方法 采用双盲、随机对照的研究方法,选择门诊及住院的三叉神经痛患者60例,随机分为卡马西平组（K组）和奥卡西平组（（）组）,各30例.比较两组治疗前和治疗后1、2、4周时疼痛发作次数、持续时间、镇痛有效率、副作用.结果 两组患者治疗后的疼痛发作次数逐渐减少、疼痛持续时间缩短及疼痛缓解程度增加,但两组治疗后同一时间的上述指标相似,K组不良反应发生率明显高于O组（P〈o.05）.结论 奥卡西平与卡马西平具有相似的治疗效果,但奥卡西平较卡马西平不良反应发生率低.     

Oxcarbazepine disposition: preliminary observations in patients

We describe a preliminary retrospective study based on the concentration of two hydroxylated metabolites of oxcarbazepine (OCZ), a new anticonvulsant substance, measured in the plasma of 15 patients with epilepsy. Their ages ranged from 8 to 68 years, 6 of them also received phenobarbital and/or phenytoin as co-medication. The concentration of 10-hydroxy-10,11-dihydrocarbamazepine (HCBZ) or of trans-10,11-dihydroxy-10,11-dihydrocarbamazepine (DHCBZ), the metabolites measured, are significantly correlated with the dose of OCZ (p less than 0.05 and p less than 0.01, respectively). DHCBZ concentrations, standardized to a constant OCZ dose or to a constant HCBZ concentration, are significantly higher during co-medication (p less than 0.01 and p less than 0.05, respectively); HCBZ levels are unaffected. These results confirm that enzyme-inducing drugs, although accelerating the oxidation HCBZ, do not induce its formation. Since HCBZ is the active metabolite, such drug interaction seems unlikely to alter OCZ pharmacological activity.     

Pharmacokinetics of New Antiepileptic Drugs

Summary: This article surveys the pharmacokinetic parameters for the new antiepileptic drugs (AEDs): felba-mate, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and vigabatrin. Compared to the pharmaco kinetics of standard AEDs, these new AEDs have progressed in terms of (a) longer half-lives, permitting once-or twice-daily dosing, (b) greatly reduced potential for drug interactions, thus increasing ease of treatment, and (c) general lack of hepatic enzyme induction, which facilitates polytherapy as well as other aspects of treatment.     

Practical Aspects of Oxcarbazepine Treatment

Summary: In patients with refractory seizures, substitution of oxcarbazepine (OCBZ) for carbamazepine (CBZ) may be associated with reduced seizure frequency and an improved mental state. The recommended dosage of OCBZ as monotherapy for adults with epilepsy is 600-1,200 mg orally per day but may be higher in patients with refractory seizures and in patients requiring combination therapy. When OCBZ is substituted for ongoing CBZ therapy, it is possible to change the dosage immediately so that the patient finishes treatment with CBZ on one day and starts with a full dosage of OCBZ on the next day, even when the full dosage is 50% greater in milligrams than the corresponding CBZ dosage. Allergic skin reactions are rare, and crossreactivity is seen in about 25% of patients hypersensitive to CBZ. Hyponatremia after the use of OCBZ is usually benign, as long as the acute water intoxication is effectively treated. Because of its pharmacokinetic advantages' and efficacy, we believe OCBZ is better than CBZ. We therefore consider OCBZ as the drug of first choice for conditions in which CBZ is currently indicated.     

Oxcarbazepine (GP 47.680): A Possible Alternative to Carbamazepine?

A double-blind randomized crossover design trial of carbamazepine (CBZ) and oxcarbazepine (OCBZ) was performed with 48 in-patients with epilepsy. All were stabilized on polytherapy including CBZ and had at least two seizures per week. CBZ was replaced by the trial medication. Each trial period started with a titration, followed by a 12-week steady state. Concomitant medications were kept constant during the trial. The criteria for assessment were seizure fit frequency and severity; tolerability; hematology and blood chemistry; plasma levels of antiepileptic drugs; EEG; cardiovascular parameters; and treatment preference. The following differences regarding OCBZ were detected: 9% reduction of the total number of seizures, with a significant reduction of tonic-clonic (20%) and tonic (31%) seizures; increased alertness and concentration ability in five patients; an allergic skin reaction with CBZ that completely disappeared in two patients while receiving OCBZ; an increase of valproate and phenytoin plasma levels in a number of patients, probably caused by reduced enzyme induction; a slight but significant reduction of serum Na, not causing clinical symptoms; less seizures than in the CBZ period in 25 patients (52%); and a preference for OCBZ in 23 patients (48%). We consider OCBZ at least as effective as CBZ with a slightly better tolerability. In severe cases, the wider therapeutic window might improve seizure control.     

奥卡西平结合心理疗法治疗青少年癫痫120例疗效观察

目的 探究心理治疗与奥卡西平结合治疗青少年癫痫的临床疗效。方法 选取海兴县医院2016年1月至2017年6月收治入院的青少年癫痫病人120例,按简单随机化分组分为治疗组和对照组两组,每组60例,随之进行一般资料的生活质量评分及症状自评得分后,对照组病人单纯口服奥卡西平,治疗组口服奥卡西平配合心理疗法,观察治疗后两组病人的临床治疗总有效率、不良反应发生率及症状自评得分情况。结果 治疗组临床总有效率95.0%(57/60)高于对照组的75.0%(45/60),治疗组治疗后症状自评得分显著高于对照组,均差异有统计学意义(P＜0.05)。治疗组的不良反应发生率(6.67%)与对照组(8.33%)比较差异无统计学意义(P＞0.05)。结论 临床采用奥卡西平配合心理疗法治疗青少年癫痫病人效果显著,为青少年癫痫病人的进一步治疗奠定了基础。