奥卡西平治疗儿童部分性发作的临床疗效及安全性观察

目的观察及评价奥卡西平（OXC）对儿童部分性发作的临床疗效和安全性。方法2006年3月-2007年5月经门诊诊断的PS／CPS或sGTCS儿童患者81例，其中27例采用奥卡西平添加治疗，54例单药治疗，经4～6周加量期和12周稳定期观察后进行评价。结果OXC添加治疗组及单药治疗组总有效率分别为81．5％和83．3％，完全控制率分别为37．0％和40．7％，且不良反应较轻，耐受性良好。结论奥卡西平治疗儿童部分性发作有效且安全，可用于儿童部分性发作的单药治疗和添加治疗。     

Hyponatremia induced by oxcarbazepine in children

We report the case of a 12-year-old girl with severe clinically relevant hyponatremia (118 mmol/l) and hypochloremia (81 mmol/l) during treatment with oxcarbazepine (OCBZ). The adverse effects were rapidly reversible after discontinuation of OCBZ and did not occur when exposed to carbamazepine. We reviewed the charts of 48 patients who received OCBZ as in-patients in our epilepsy centre and found hyponatremia in nine and hypochloremia in four. The mean sodium level of all patients was 139 mmol/l (range 118–150 mmol/l). We did not see any correlation between sodium or chloride levels and dose of OCBZ or blood serum level of the active metabolite 10-OH-carbazepine. We emphasize that children are at risk of developing electrolyte disturbances during treatment with OCBZ and thus the level of at least sodium should be monitored in those patients.     

奥卡西平治疗癫痫的临床观察

目的 观察奥卡西平（OCBZ）治疗癫痫的疗效、耐受性和安全性。方法 68例癫痫患者采用开放性自身对照研究,其中36例进入单药治疗组,32例进入添加治疗组。剂量为0.15～0.3g,分早晚两次,维持剂量每天600～1200mg,最大未超过1.8g;儿童按10mg/kg/d,分两次服用,增加剂量每周不超过10mg/kg/d。分两次服用,最大不超过35mg/kg/d。分析两组24周以上的疗效、不良反应、耐受性和安全性。结果 本组总有效率为85.3%,完全控制为36.8%;其中单药治疗组控制率44.4%,总有效率为91.7%,添加治疗组控制率为28.1%,总有效率为78.1%。最常见的副及应为头昏、头痛、嗜睡、皮疹、纳差等,单治组副反应总发生率为30.6%,添加组副反应发生率为53.1%,两组比较,添加治疗组出现的反应相对多于单药治疗组。两组耐受性好,安全性高。结论 奥卡西平治疗癫痫安全、稳定、有效。     

Isobolographic characterisation of interactions among selected newer antiepileptic drugs in the mouse pentylenetetrazole-induced seizure model

The aim of this study was to characterise the types of interactions between gabapentin (GBP), tiagabine (TGB) and three second-generation antiepileptic drugs (AEDs) with different mechanisms of action (felbamate [FBM], loreclezole [LCZ], and oxcarbazepine [OXC]) by isobolographic analysis. Anticonvulsant and acute neurotoxic adverse effect profiles of combinations of GBP and TGB with other AEDs at fixed ratios of 1:3, 1:1 and 3:1 were investigated in pentylenetetrazole (PTZ)-induced seizures and the chimney test (as a measure of motor impairment) in mice so as to identify optimal combinations. Protective indices (PIs) and benefit indices (BIs) were calculated for each combination in order to properly classify the investigated interactions. Isobolographic analysis revealed that only the combination of GBP with OXC at the fixed ratio of 1:1 exerted supra-additive (synergistic) interaction (P<0.05) against PTZ-induced seizures. The other combinations tested between GBP and OXC (1:3 and 3:1), as well as all combinations of GBP with FBM or LCZ (1:3, 1:1 and 3:1) were additive in the PTZ test. Similarly, all combinations of TGB with FBM LCZ, and OXC (at the fixed ratios of 1:3, 1:1 and 3:1) were associated with additive interactions against PTZ-induced seizures in mice. In the chimney test, the isobolographic analysis revealed that the combinations of GBP and OXC (at the fixed ratios of 1:3 and 1:1), GBP and LCZ (at 1:1), as well as TGB and OXC (at 1:3 and 1:1) were sub-additive (antagonistic; P<0.05 and P<0.01). In contrast, only one combination tested (TGB and LCZ at the fixed ratio of 1:1) was supra-additive (synergistic; P<0.05) in the chimney test, whereas the other combinations of GBP and TGB with OXC, FBM, and LCZ displayed barely additivity. Based upon the current preclinical data, GBP and OXC appear to be a particularly favourable combination. Also, the combinations of GBP with FBM, GBP with LCZ, and TGB with OXC are beneficial. In contrast, during the combining of TGB with FBM, or TGB with LCZ, the utmost caution is advised because of their unfavourable profiles in this preclinical study.The results of this study were presented in part at the Thirty years of cooperation between German and Polish pharmacologists, new perspectives in the common Europe—Bialowieza, Poland, 18–21 September 2003 (abstract in Pol J Pharmacol (2003) 55:500–501).     

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。     

奥卡西平联合神经阻滞治疗原发性三叉神经痛的临床疗效

目的：分析奥卡西平联合神经阻滞治疗原发性三叉神经痛的临床疗效。方法选择2011-02-2013-09在我院接受诊治的原发性三叉神经痛患者94例,按照随机数字表法分为对照组（n＝47）与治疗组（n＝47）。对照组给予奥卡西平治疗,治疗组在奥卡西平治疗基础上采取神经阻滞治疗。结果治疗组治疗后1 d、3周、6周NRS评分均明显低于对照组（P＜0.05）;治疗组总有效率91.49％,显著高于对照组的78.72％,差异有统计学意义（ P＜0.05）;治疗组不良反应显著低于对照组,差异有统计学意义（ P＜0.05）。结论奥卡西平联合神经阻滞治疗原发性三叉神经痛疗效显著,且不良反应较轻,具有重要临床价值。     

小儿抗痫胶囊联合奥卡西平治疗小儿癫痫的疗效观察

目的 探讨小儿癫痫应用小儿抗痫胶囊联合奥卡西平片治疗的临床效果。方法 选取2016年1月—2018年8朝阳市第二医院收治的150例小儿癫痫患者,运用随机数字表法将其随机分成观察组（n=75）和对照组（n=75）。对照组患者口服奥卡西平片,以10 mg/（kg·d）为起始剂量,而后每隔1周,增加剂量10 mg/（kg·d）,直至维持剂量30 mg/（kg·d）,均分早晚2次给药。观察组在对照组基础上口服小儿抗痫胶囊,8粒/次,3次/d。连续治疗6个月。对比两组临床疗效,治疗前后癫痫计分、发作频率、持续时间、痫性放电比率、儿童生活质量量表（Peds QLTM4.0）普适型家长代评量表评分及韦氏儿童智力量表第四版（WISC-Ⅳ）评分变化。结果 治疗后,观察组总有效率为93.3%,较对照组81.3%显著增加（P<0.05）。与治疗前相比,两组治疗后癫痫发作情况（包括意识状态及意识障碍、强直、阵挛的持续时间和脑电图）计分及其总分均显著下降（P<0.05）;但观察组减少更显著（P<0.05）。两组治疗后发作频率、痫性放电比率均较治疗前显著降低,而持续时间均显著缩短（P<0.05）;且观察组改善更显著（P<0.05）。两组治疗后Peds QLTM4.0普适型家长代评量表中各维度（生理功能、社交功能、学校表现、情感功能）评分及其总分均较治疗前显著升高（P<0.05）,而观察组上升更显著（P<0.05）。两组治疗后WISC-Ⅳ中各指数（语言理解、知觉推理、工作记忆、加工速度）评分及总智商评分均显著高于治疗前（P<0.05）,且观察组增高更显著（P<0.05）。结论 小儿癫痫应用小儿抗痫胶囊联合奥卡西平片治疗的整体效果显著,可明显稳定患儿病情,控制癫痫发作,减少痫性放电,提高患儿生活质量及智力水平,且安全性较高。     

Clinical Pharmacology and Pharmacokinetics of Oxcarbazepine

Summary: Oxcarbazepine (OCBZ) is a new antiepileptic drug (AED) structurally related to carbamazepine (CBZ) but differing in several important aspects, notably metabolism and induction of metabolic pathways. Consequently, OXCB has fewer drug-drug interactions compared with CBZ. Absorption of OCBZ is rapid and complete. In animals it is responsible for the pharmacological effect. In humans, however, the parent compound is rapidly and extensively metabolized to a monohydroxy derivative (MHD), which is responsible for the therapeutic effect. Exposure to the MHD increases dose proportionally, and steady state is achieved after only three or four doses in a twice-daily regimen. When given with food, systemic exposure to MHD increases by about 17%. MHD is eliminated with a half-life of about 8–10 h. About 27% of the dose is recovered in the urine as unchanged MHD and a further 49% as a glucuronide conjugate of MHD. Results suggest that the kinetics of OCBZ should not be affected by impaired liver function. Impaired kidney function does not affect the kinetics of MHD; the glucuronide conjugate will, however, accumulate in these patients. The conversion of OCBZ to MHD is catalyzed by reductase enzymes, which are not subject to induction. Furthermore, OCBZ itself does not appear to induce the cytochrome P-450 family in general, although it does induce the P-450IIIA subfamily; which is responsible for the metabolism of estrogens and the dihydropyridine calcium-channel blockers (e.g., nifedipine, felodipine). In patients, linear and dose-proportional kinetics with no autoinduction of metabolism simplify OCBZ dosage adjustment.     

The effect of renal impairment on the pharmacokinetics of oxcarbazepine and its metabolites

We have studied the effect of renal impairment on the pharmacokinetics of oxcarbazepine, its active monohydroxy-metabolite (which predominates in plasma), their glucuronides, and the inactive dihydroxy-metabolite after a single oral dose of oxcarbazepine (300 mg). Six subjects with normal renal function and 20 patients with various degrees of renal impairment participated.The mean areas under the plasma concentration-time curves of oxcarbazepine and its monohydroxy-metabolite were 2–2.5-times higher in patients with severe renal impairment (CL_CR<10 ml·min^–1) than in healthy subjects. The apparent elimination half-life of the monohydroxy-metabolite [19 (SD 3) h] in these patients was about twice that in healthy subjects.The effect of renal impairment on the plasma concentrations of glucuronides was more marked. The renal clearances of the unconjugated monohydroxy-metabolite and its glucuronides (the main compounds recovered in urine) correlated well with creatinine clearance.The maximum target dose in patients with slight renal impairment (CL_CR>30 ml·min^–1) should not be changed. In patients with moderate renal impairment (CL_CR10–30 ml·min^–1) it should be reduced by 50%. In patients with severe renal impairment (CL_CR<10 ml·min^–1), the glucuronides of oxcarbazepine and its monohydroxy-metabolite are likely to accumulate during repeated administration, and dosage adjustment of oxcarbazepine in these patients could not be proposed from this single administration study.     

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.