托吡酯治疗小儿癫32例

目的 :评价托吡酯治疗小儿癫的疗效和安全性。方法 :3 2例癫患儿口服托吡酯 ,起始剂量为 0 .8～1.2mg·kg 1·d 1,qd或bid ,目标剂量为 4～ 9mg·kg 1·d 1,bid。随访时间为 3～ 9个月。结果 :托吡酯治疗小儿癫的总有效率 71.9% ,副作用较轻。结论 :托吡酯治疗小儿癫有较好的疗效 ,患儿对其有较好的耐受性     

托吡酯与丙戊酸钠对照治疗成人癫痫124例

目的:观察托吡酯及丙戊酸钠单药对照治疗新诊断的成人癫痫患者的疗效及耐受性。方法:入组患者124例,其中试验组60例,起始剂量25 mg·d-1,qd,对照组64例,起始剂量丙戊酸钠200 mg·d-1,bid。根据患者发作情况及药物不良反应调整剂量,观察药物的疗效及耐受性,以达最佳或最终剂量。通过比较2组患者治疗前后的月平均发作次数和退出试验的病例比例评价药物的总体疗效。结果:观察时间试验组(8．10±6．44)个月,对照组(14．16±11．75)个月。最佳或最终剂量范围试验组50～300 mg·d-1。对照组200～1500 mg·d-1。两组总有效率分别为78．33％及59．38％,两组比较差异有显著性(P=0．0383)。试验组和对照组分别有2例和1例因不良反应退出或换药。结论:托吡酯单药治疗成年新诊断癫痫患者的疗效好于丙戊酸钠,具有较好的安全性和耐受性。     

托吡酯与卡马西平治疗躁狂发作的疗效比较

目的 :比较托吡酯与卡马西平治疗躁狂发作的疗效及安全性。方法 :6 0例躁狂发作病人分为 2组 ,托吡酯组 30例给予托吡酯 ,开始剂量 2 5mg·d- 1,2wk内逐渐增加至 10 0～ 4 0 0mg·d- 1;卡马西平组 30例给予卡马西平 ,开始剂量 0 .1g·d- 1,2wk内逐渐增加至 0 .4～ 1.0 g·d- 1,疗程均 6wk。用BRMS评定疗效 ,TESS评定不良反应。结果 :托吡酯组有效率 6 1% ,卡马西平组 6 2 % ,2组疗效无明显差异 (P >0 .0 5 )。托吡酯组常见的不良反应是胃肠症状 ,除体重下降外 ,与卡马西平组无显著差异。结论 :托吡酯治疗躁狂发作安全有效 ,疗效与卡马西平相似。     

托吡酯与丙戊酸钠缓释片治疗难治性癫痫疗效比较

目的 :比较托吡酯与丙戊酸钠缓释片治疗难治性癫痫的疗效。方法 :托吡酯组 39例 ,丙戊酸钠组 4 1例 ,托吡酯成人及儿童剂量在约 2mo中逐渐增至 2 0 0mg·d- 1及 4mg·kg·d- 1左右 ,po ,bid。丙戊酸钠缓释片成人剂量 0 .5～ 1.0 g·d- 1,儿童剂量逐增至总量 15～ 30mg·kg·d- 1,为每日清晨或早晨、中午 2次服用。治疗 4mo及 6mo后评定疗效。结果 :托吡酯组治疗 6mo的继发性全身发作 ,简单及复杂性部分发作有效例数优于丙戊酸钠组 ,4例在加药期快时出现疲劳、嗜睡、注意力不集中等。丙戊酸钠组 1例发生骨髓造血功能严重低下。结论 :托吡酯治疗难治性癫痫简单及复杂部分性发作伴或不伴继发性全身发作疗效优于丙戊酸钠 ,无骨髓抑制 ,也无肝、肾功能损伤     

托吡酯治疗成人癫痫部分性发作

目的 :观察托吡酯单药和与不同抗癫痫药(AEDs)合用治疗成人癫痫部分性发作疗效、剂量和不良反应的关系。方法 :A组 (n =31)托吡酯与酶诱导剂AEDs合用 ;B组 (n =19)托吡酯与非酶诱导剂AEDs合用 ;C组 (n =5 1)单用托吡酯。托吡酯剂量为 :开始 12 .5～ 2 5mg·d- 1,每周根据疗效增加12 .5～ 2 5mg·d- 1,分 2次口服 ,共 2 0wk。观察各组疗效、剂量和不良反应。结果 :A组有效率 61%,B组为 68%,C组为 88%,A和B组疗效相似 ,P >0 .0 5 ;C组疗效高于A和B组 ,P <0 .0 5。 3组间有效治疗剂量差异无显著意义。不良反应率A组38%,B组 2 1%,C组 31%,P >0 .0 5 ,2例合用卡马西平出现严重精神症状。结论 :托吡酯是治疗癫痫部分性发作有效药物 ,与不同AEDs合用在疗效、剂量和不良反应方面差异无显著意义。中枢神经系统少见严重不良反应 ,但值得重视。     

托吡酯单药或添加治疗儿童各型癫痫的临床观察

目的:研究托吡酯单药或添加治疗小儿癫痫的疗效与安全性.方法:选取100例癫痫患儿,其中52例原来使用的抗癫痫药种类和剂量不变,将托吡酯作为辅助治疗药物,从0.50～1.00 mg/(kg·d)开始,每周增加0.50～1.00 mg/(kg·d),目标剂量4.00～8.00 mg/(kg·d),根据癫痫发作情况调整托吡酯剂量.48例未使用过抗癫痫药物治疗的癫痫患儿单用托吡酯治疗,起始剂量为1.5 mg/(kg·d),每周增加0.50～1.00 mg/(kg·d),目标剂量8.00 mg/(kg·d).结果:添加治疗组有效率71.15%,单药治疗组有效率87.50%,均显示较好疗效,两组不良反应均较少且轻微.结论:托吡酯单药治疗和作为添加药物治疗小儿各型癫痫发作均有较好的疗效,不良反应较少.     

托吡酯单药与添加治疗婴儿痉挛综合征的对照观察

目的:研究早期有效控制婴儿痉挛综合征(west综合征)的理想药物.方法:应用托吡酯 (TPM)治疗28例患儿, 其中初治单用托吡脂治疗18例,其它方案治疗效果不佳添加托吡酯治疗10例.结果:托吡酯早期单药治疗完全控制发作11例,晚期添加治疗2例,统计学处理差异有显著性 (P<0.05),单药治疗显效时间(12.3±7.1)d,有效剂量(3.0±1.4)mg·kg-1·d-1,较添加组(33.0±12) d、(6.8±2.04) mg·kg-1·d-1显效快,有效剂量小,统计学处理差异有显著性 (P<0.01).结论:TPM治疗west综合征早期,单药较晚期添加效果好,对west综合征一经确诊可早期选择TPM治疗.     

托吡酯治疗儿童抽动秽语综合征

目的:观察托吡酯治疗儿童抽动秽语综合征(Tourettesyndrome, TS)的疗效及其不良反应。方法:将96例TS病儿分为治疗组和对照组各48例。治疗组采用托吡酯按0. 5 ~ 1. 5mg·kg-1·d-1,分2 次口服, 对照组采用硫必利100 ~400mg·d-1,分2~3次口服,疗程6mo。治疗期间每月定期门诊复诊。结果:治疗组有效率为87 %,对照组有效率为85 %。2组疗效比较差异无显著意义(P> 0. 05); 2组不良反应率相比有非常显著差异(P <0. 01)。结论:托吡酯与硫必利治疗TS疗效相似,且不良反应较硫必利明显减少,同时可有效减轻合并症状。     

托吡酯治疗脑梗死性癫32例

目的评价托吡酯治疗脑梗死性癫患者的疗效与安全性。方法将52例脑梗死性癫患者随机分为治疗组32例和对照组20例，治疗组给予托吡酯片口服，每次25 mg·d-1， bid，持续7 d，以后按每周25～50 mg·d-1的量逐渐增加，依临床疗效调整剂量，最大剂量为375～500 mg·d 1；对照组给予卡马西平片口服，每次0.1 g，tid，逐渐加量，依临床疗效调整剂量，最大剂量为1.0～1.2 g·d 1。两组观察期均为20周。结果治疗组总有效率（84.4%）明显高于对照组（60.0%）（P＜0.05）。治疗组中小面积梗死的总有效率（95.5%）明显高于大面积梗死患者（60.0%）（P＜0.05）。治疗组不良反应发生率21.9%，对照组不良反应发生率40.0%，不良反应均随着治疗时间的延长而消失。结论托吡酯单药治疗脑梗死性癫患者疗效较好，安全，尤其对小面积脑梗死型癫疗效较好。     

托吡酯加用治疗难治性癫痫发作218例的多中心临床研究

目的 :观察托吡酯加用治疗多种类型癫痫发作的临床疗效。方法 :2 18名癫痫病人 ,均为用过各种抗癫痫药物治疗效果不佳的难治性癫痫 ;采用逐渐加量法 ,加量期 8wk ,托吡酯开始剂量为 2 5mg·d- 1,目标剂量为 2 0 0mg·d- 1,观察 12wk后进入延长期。结果 :治疗后 ,2 6例病人 (12 .3% )发作完全消失 ,5 9例 (2 8.0 % )发作减少≥ 75 % ;10 7例(5 0 .7% )发作减少≥ 5 0 %～ <75 % ;19例(9 .0 % )无效。 5例 (2 .3% )因严重不良反应而中断治疗。 2例失访 (原因不明 )。结论 :托吡酯是一种非常有效的新型抗癫痫药物 ,值得临床推广使用     

单用不同剂量托吡酯与卡马西平治疗老年癫痫发作的疗效比较

目的:观察单用不同剂量托吡酯及卡马西平治疗老年癫痫病人的临床疗效和不良反应,探讨单用托吡酯更安全、更有效的给药方法。方法:老年癫痫病人120例,分为卡马西平组,31例,服用卡马西平(200～ 600 mg·d~(-1));单用托吡酯组,89例病人按服药剂量不同又分为,低剂量组47例(托_1组,100～200 mg·d~(-1)),高剂量组42例(托_2组,300～400 mg·d~(-1)):结果:托_1,组总有效率81％,托_2组总有效率74％;卡马西平组总有效率77％,3组比较无显著差异(P>0．05)。托_2组不良反应发生率(57％)高于托_1组(34％)(P<0．05)。托吡酯组主要不良反应为感觉异常、胃纳差、头痛、嗜睡头晕和体重减轻。结论:单用较小剂量托吡酯(100～ 200 mg·d~(-1))治疗老年癫痫发怍,疗效好,不良反应少而且轻。     

托吡酯单药治疗癫痫有效性和安全性的长期临床研究

目的评价托吡酯(topiram ate)单药治疗成人及儿童癫痫患者的长期疗效和安全性。方法58例癫痫患者(成人32例,儿童26例)为新诊断癫痫(45例),或原服用1种抗癫痫药仍发作(13例)。采取托吡酯小剂量开始逐渐添加的开放性自身对照研究,第8周达最大耐受量。以后13例逐渐减原服抗癫痫药。托吡酯维持最大耐受量观察1～3年或以上。评定托吡酯的长期疗效和安全性及其与剂量的关系。结果托吡酯治疗6个月时成人组与儿童组有效率比较差异无统计学意义。治疗第8周、6个月、1年、2年和3年的有效率分别为54%、69%、74%、80%、77%,发作控制率分别为30%、39%、37%、46%、47%。部分性发作有效率(70%)与全面性发作的有效率(43%)比较差异无统计学意义(P>0.05)。连续发作控制2年以上者12例(34%)。有效组维持剂量成人为(124±55)m g/d,儿童为(2.8±1.3)m g.kg-1.d-1。第1、2、3年坚持托吡酯单药治疗者分别占73%、60%和57%。18例(31%)出现不良反应,大部分出现在添加期,最常见的不良反应为胃纳差、体重减轻和反应迟钝。观察满3年因不良反应退出2例(7%),因疗效不佳退出6例(20%)。结论托吡酯单药治疗癫痫长期有效和安全,采取个体化治疗可减轻不良反应。     

Topiramate: a review of its use in childhood epilepsy

Topiramate is an antiepileptic drug (AED) which appears to have a broad range of antiseizure activity in humans. A previous overview focused primarily on results of trials of topiramate in adults with epilepsy, and this review highlights the use of topiramate in children. Clinical trials have shown that topiramate is effective when used adjunctively in children with refractory partial-onset seizures and generalised tonic-clonic seizures. The drug significantly reduced seizure frequency compared with placebo in children with partial-onset epilepsy after 16 weeks of double-blind adjunctive treatment (33.1 vs 10.5%); the frequency of secondarily generalised seizures was also markedly reduced. During a nonblind extension of this trial, the mean dosage was titrated from 4.8 to 9 mg/kg/day and further reductions in the frequency of seizures were observed (71% compared with prestudy levels). In 2 mixed adult/paediatric populations with primary generalised tonic-clonic seizures, topiramate (target dosage 5.2 to 9.3 mg/kg/day) reduced the seizure rate compared with those receiving placebo. This difference was significant in one trial (56.7 vs 9%) but not in another (57.1 vs 33.2%). A subanalysis of the paediatric patients found that the favourable effect of topiramate on seizure rates was not age-related. Topiramate (median average dosage 5.1 mg/kg/day) was also found to be useful as adjunctive therapy in the management of Lennox-Gastaut syndrome and significantly reduced the mean frequency of drop attacks by 14.8% compared with an increase of 5.1% with placebo. Further gains in seizure control were made in a nonblind extension of this trial where the mean topiramate dosage was 10 mg/kg/day. Nine of 11 patients in 1 pilot trial of children with otherwise intractable West syndrome, and 5 of 10 in another, achieved a > or =50% reduction in seizure rate with topiramate (target dosage up to 24 mg/kg/day). In an 18-month extension of the former trial (mean dosage 29 mg/kg/day) a > or =50% reduction in seizures was maintained in 7 of 11 children. Adverse events associated with adjunctive topiramate therapy in children were predominantly neuropsychiatric and generally mild to moderate in severity. Behavioural and cognitive problems do occur and are a limiting factor in some children. Also, weight loss can be problematical in some individuals. Withdrawal rates were low in the controlled trials (4.8%), but appear to be more frequent in noncomparative and post-marketing studies. CONCLUSION: Well controlled studies have demonstrated that topiramate is an effective agent for the adjunctive therapy of partial and generalised tonic-clonic seizures in children. Treatment-limiting adverse events do occur, but these may be managed by slow titration. Although comparative studies with the other newer AEDs used in adjuntive therapy are required, topiramate is an important extension to the range of drugs that may be used to treat refractory epilepsy in children.     

Tolerability and safety of topiramate in Chinese patients with epilepsy : an open-label, long-term, prospective study

OBJECTIVES: This study focused on (i) evaluating the long-term tolerability and safety of topiramate in Chinese patients with epilepsy, and (ii) comparing the tolerability and safety of topiramate monotherapy versus polytherapy in the same population. METHODS: This was a prospective, open-label, long-term (36 months) clinical trial. 320 patients (275 adults and 45 children) with epilepsy were recruited into the study; of these, 156 patients had generalised seizures, 151 patients had partial seizures and 13 patients had unclassifiable seizures. All patients received topiramate approximately 200 mg/day either as monotherapy or as adjunctive therapy. At each visit, a physical examination and routine laboratory analysis were performed, and the adverse event (AE) profile was obtained by face-to-face interview. RESULTS: 268 patients received topiramate 相似文献   

用蒙特卡洛模拟优化耐甲氧西林金黄色葡萄球菌感染的肾功能不全低龄患儿万古霉素的给药方案

目的 应用蒙特卡洛模拟评价万古霉素在肾功能正常与不全低龄耐甲氧西林金黄色葡萄球菌(MRSA)感染患儿中的给药方案.方法 收集2013—2014年成都地区万古霉素对MRSA菌株的最低抑菌浓度值(MIC)和其在2个月 ～2岁中国低龄患儿中药动学资料,经Crystal Ball软件模拟5000例次得到相应目标获得概率(PTA)与累计反应分数(CFR).结果 万古霉素对MRSA的MIC分布频率,MIC为0.03、0.06、0.12、0.25、0.50 mg·L-1时各占12.79％,MIC为1、2 mg·L-1时各占29.07％ 、6.98％.万古霉素达满意抗菌活性的最低剂量:肾功能正常者(A组),MIC为0.03～0.06、0.12和0.25 mg·L-1时分别予30、37.5和80 mg·kg-1·d-1,MIC为0.5～2 mg·L-1时即使80 mg·kg-1·d-1也不能达满意抗菌活性;肾功能轻度不全者[B组,估算的肾小球滤过率(eGFR)为60～89 mL·min-1·1.73 m-2],MIC为0.03～0.12、0.25和0.5 mg·L-1时分别予30、40和80 mg·kg-1·d-1,MIC为1～2 mg·L-1时即使80 mg·kg-1·d-1也不能达满意抗菌活性;肾功能中度不全者(C组,eGFR为30～59 mL·min-1·1.73 m-2),MIC为0.03～0.25、0.5 mg·L-1时分别予30、50 mg·kg-1·d-1,MIC为1～2 mg·L-1时即使80 mg·kg-1·d-1也不能达满意抗菌活性.各方案下A、B组对MRSA的CFR均<90％.结论 感染MR-SA的肾功能正常与轻度不全低龄患儿经验性应用万古霉素时可考虑联合用药,结合各MIC分布频率和达满意抗菌活性的最低剂量可知,大多数肾功能正常低龄患儿按40 mg·kg-1·d-1给药剂量偏低,绝大多数肾功能中度不全者应用50～80 mg·kg-1·d-1可获得满意抗菌活性.     

雷公藤内酯醇抑制同种异体皮肤移植物排异反应

目的：观察雷公藤二萜类化合物主要成分之一的雷公藤内酯醇（又称雷公藤甲素）对同种异体皮肤移植物存活时间的影响。方法：以环孢霉素Ａ（ＣｓＡ）为阳性对照。结果：雷公藤内酯醇可以明显地延长同种异体皮肤移植物的存活时间，其药理作用与该药的剂量和给药时间密切相关。作者还首次观察到小剂量雷公藤内酯醇和ＣｓＡ联合使用能非常明显地延长皮肤移植物的存活时间。结论：雷公藤内酯醇在移植的抗排异反应治疗中有非常好的应用前景。     

Oxcarbazepine: a review of its use in children with epilepsy

Oxcarbazepine (Trileptal, Timox) is structurally related to carbamazepine and has anticonvulsant activity. Studies suggest that the anticonvulsant activity of oxcarbazepine is mediated via the blocking of neuronal ion channels. In patients aged <18 years, the efficacy of oxcarbazepine monotherapy was similar to that of phenytoin in children with partial onset or generalized tonic-clonic seizures in a 48-week trial. Additional supporting findings demonstrated that 43-71% of patients with partial onset, generalized or undetermined epilepsy were seizure free after oxcarbazepine monotherapy (mean dosage 27.7-50 mg/kg/day; duration 1-5 years). In contrast, one small nonblind trial showed more patients treated with oxcarbazepine monotherapy than with carbamazepine monotherapy had recurrent seizures during 16 months of therapy (although the conclusions that can be drawn from this trial are limited). As adjunctive therapy, oxcarbazepine was significantly better than placebo at reducing seizure frequency in children and adolescents with refractory partial onset seizures with or without secondary generalization: the median percentage change in partial onset seizure frequency was 35% vs 9%, respectively, during 16 weeks of therapy. In noncomparative trials of adjunctive oxcarbazepine (mean dosage of 34.5-56.7 mg/kg/day), 7-11% of patients with partial onset or generalized seizures were seizure free during treatment, and 20-54% had seizure reductions of > or=50%. Oxcarbazepine was generally well tolerated during monotherapy and adjunctive therapy; 2.5% and 10% of patients withdrew from well controlled trials of oxcarbazepine monotherapy and adjunctive therapy. Oxcarbazepine monotherapy was better tolerated than phenytoin and events observed in oxcarbazepine-treated patients were transient. Oxcarbazepine metabolism is largely unaffected by induction of the cytochrome (CYP) P450 system. However, oxcarbazepine can inhibit CYP2C19 and induce CYP3A4 and CYP3A5, thereby interfering with the metabolism of other drugs (e.g. phenytoin). In addition, oxcarbazepine decreases plasma levels of oral contraceptives and alternative contraceptive methods should be used. In conclusion, oxcarbazepine (as both monotherapy and adjunctive therapy) has shown efficacy in the treatment of partial onset seizures in children with epilepsy. Nevertheless, the generally favorable tolerability profile and relatively low potential for drug interactions of oxcarbazepine make it a valuable option in the treatment of childhood epilepsy.