新型抗癫痫药的安全性评价

新型抗癫痫药与传统抗癫痫药相比,具有较理想的药代动力学特性,不良反应和药物相互作用较少,耐受性和安全性较好。由于新型抗癫痫药上市时间较短,临床资料和用药经验相对较少,其安全性问题尤其值得人们关注。本文对9种新型抗癫痫药从作用机制、药代动力学、不良反应、相互作用等方面作一综合评价。     

儿童抗癫痫药物的血药浓度监测

目的儿童抗癫痫药物的血药浓度测定可提高疗效，减少毒副作用，指导临床合理使用抗癫痫药物。方法对单种药和两药联用的８６例癫痫患儿，用荧光偏振免疫法（ＦＴＩＡ）和稳态血药浓度一点法监测血药浓度并进行疗效分析。结果单用一药能控制症状不宜并用两药；必须两药联用时应注意药物相互作用。结论儿童的抗癫痫药物的血药浓度监测，能及早发现不易觉察的中毒，并结合疗效调整给药剂量与方法。     

传统和新型抗癫痫药的合理选择

目的:面对日益复杂的抗癫痫药应用状况,对传统及新型抗癫痫药的临床应用状况进行评价以期为临床合理用药提供参考。方法:从6个传统抗癫痫药和9个新型抗癫痫药的临床适应证及其药动学特点、不良反应和药物相互作用,患者的年龄、性别和疾病状态以及经济因素等方面对影响抗癫痫药合理选择的因素作一探讨。结果及结论:传统抗癫痫药仍被广泛应用,新型抗癫痫药与传统抗癫痫药相比具有药代动力学更好、药物相互作用更少、耐受性更好等优势,但临床资料和用药经验相对缺乏,临床应用时应权衡利弊,合理选择。     

癫痫病药物治疗新进展

综述近年出现的一些新型抗癫痫药的作用机制、药动学、用法用量、药物不良反应、药物相互作用及临床治疗应遵循的原则,为临床合理应用抗癫痫药提供用药依据.     

新型抗癫痫药之间及其与传统抗癫痫药的相互作用和机制*

分别综述了几种新型抗癫痫药（托吡酯、非氨酯、奥卡西平、拉莫三嗪、唑尼沙胺、左乙拉西坦、噻加宾、加巴喷丁及氨己烯酸）与传统抗癫痫药联合应用时以及这些新型抗癫痫药之间的相互作用及其发生机制，阐明细胞色素P450酶和葡萄糖苷酸转移酶在新型抗癫痫药的相互作用中的意义及重要性。为临床合理联合应用提供理论依据，提高抗癫痫治疗的可靠性、安全性和有效性。     

托吡酯临床研究和应用进展

托吡酯是一种新型的抗癫痫药物，具有多重抗癫痫作用机制。托吡酯吸收迅速完全，呈线性药物动力学特征。生物利用度高，血浆T1/2长，每日服药2次，托吡酯与其他抗癫痫药物相互作用小，可作为单药或作为添加药，对儿童，成年人的多种类型癫痫具有良好临床治疗效果。不良反应较小，病人易于耐受。     

抗癫痫药物的相互作用

抗癫痫药物的相互作用安儒峰王立兰董进和郭丰广（泰山医学院附属医院泰安２７１０００）多数癫痫患者需长期服用抗癫痫药物来控制病情，而抗癫痫药物（ＡＥＤ）间的相互作用错综复杂，故安全合理地使用ＡＥＤ是药物治疗癫痫的关键。本文着重介绍近年来新发展的ＡＥＤ间的...     

新型抗癫痫药

近２０年来主要发展了两类抗癫痫药：（１）增强大脑γ－氨基丁酸活性的药物；（２）抑制有兴奋作用的氨基酸的药物；奥卡西平和卡马西平的作用机理相同，而加巴喷丁的作用机理示明。这些新抗癫痫药的主要临床适应证为复杂的局限性癫痫发作，副作用较轻，多数为中枢神经系统反应。     

儿童抗癫痫药过敏反应36例

抗癫痫药过敏反应是一种抗癫痫药所致的药物剂量无关的副反应,多为皮疹、发热、淋巴结肿大、内脏损害等表现,多见于服用芳香族抗癫痫药（如苯巴比妥、苯妥英钠及卡马西平等）的患者。其中部分病例可以表现为抗癫痫药过敏综合征（antiepileptic drug hypersensitive syndrome,AHS）,临床主要表现为发热、皮疹和内脏损害。抗癫痫药过敏反应早期临床表现各异,如不重视易延误诊断加重病情,一旦出现严重肝损害、     

哪些药品容易出现药物相互作用？

治疗窗范围窄的药物（即剂量稍有变化药理作用即有明显改变的药物）,需要监测血药浓度的药物,酶诱导剂和酶抑制剂都容易发生药物相互作用。它们包括口服抗凝药、口服降糖药、抗生素类、抗癫痫药、抗心律失常药、强心苷和抗过敏药等。     

Gabapentin: new indication. In postherpetic neuralgia when amitriptyline fails

(1) Postherpetic pain is infrequent, but the incidence increases with age. (2) The reference treatment for postherpetic pain is oral amitriptyline or desipramine. (3) Gabapentin, an antiepileptic agent, is the first drug to be granted specific approval in France for the treatment of postherpetic pain. (4) In two placebo-controlled trials, gabapentin at a dose of between 1 800 and 3 600 mg/day halved the intensity of pain in about one in three patients. In comparison, pain improved in about 50% of patients taking amitriptyline in clinical trials. (5) Both gabapentin and amitriptyline provoke sedation, but dizziness and peripheral oedema are more frequent on gabapentin, while atropinic effects predominate with amitriptyline. (6) Daily treatment is 10 times more costly in France. (7) In practice, the standard treatment of postherpetic pain remains oral amitriptyline or desipramine. Gabapentin is an alternative, given its different safety profile.     

Gabapentin Extended-Release - Depomed: Gabapentin ER, Gabapentin Gastric Retention, Gabapentin GR

Depomed is developing an extended-release (ER) oral formulation of gabapentin, a GABA receptor agonist commonly used for the treatment of epilepsy and seizures, neuropathic pain and hot flushes. Gabapentin ER is based on the company's proprietary AcuForm drug delivery technology, which is part of the Gastric Retention (GR) family of technologies; this offers improved drug absorption and bioavailability compared with the existing immediate-release formulation of gabapentin (Neurontin), making gabapentin ER suitable for twice-daily dosing. The product is in clinical development for the treatment of postherpetic neuralgia and diabetic neuropathies in the US. Additionally, Depomed has commenced a phase II trial of gabapentin ER in postmenopausal patients with hot flushes. Depomed's AcuForm platform is based on polymer technology that provides targeted drug delivery for a variety of compounds. Following ingestion, AcuForm tablets swell and are retained for 6-8 hours in the stomach, enabling controlled and prolonged release of gabapentin to the upper intestinal tract; this extends the time of drug delivery to the small intestine for complete and safe elimination via the lower intestinal track. Gabapentin ER is available for licensing. Depomed acquired exclusive development and commercialisation rights to gabapentin ER in September 2003 via its subsidiary, Depomed Development Ltd (DDL). Depomed is not required to pay upfront license fees, but will make royalty and milestone payments to DDL upon successful commercialisation of gabapentin ER. Gabapentin ER was originally developed by DDL, a joint venture between Depomed and Elan established in January 2000 to design products using the GR family of technologies. However, in efforts to restructure joint venture relationships, Elan withdrew from operational involvement of DDL in September 2003, and Depomed has gained full ownership of DDL. Depomed sublicensed exclusive rights to a US patent (held by the University of Rochester) covering the use of gabapentin in the treatment of hot flushes from PharmaNova in October 2006. Under the agreement, Depomed paid PharmaNova an upfront fee of US dollars 500 000. PharmaNova is also entitled to milestone payments and royalties on sales of gabapentin ER in this indication only. Depomed has reported significant safety and efficacy benefits from gabapentin ER in its phase II trial. This study was initiated in February 2005 following positive results from a phase I trial in which gabapentin ER demonstrated a pharmacokinetic profile suitable for twice-daily dosing. In two pharmacokinetic studies, gabapentin ER achieved improved bioavailability at higher doses. This result supports Depomed's development of a once- or twice-daily product with potentially fewer adverse events. The basic US patents relating to gabapentin expired in 2000. Depomed holds exclusive rights to a US patent (No. 6 310 098) held by the University of Rochester covering the use of gabapentin to treat hot flushes.Additionally, Depomed was issued a US patent (No. 6 723 340) in May 2004 that covers proprietary polymer combinations (as used in AcuForm tablets) to create improved formulations of existing drugs.     

Effects of gabapentin on cocaine self-administration, cocaine-triggered relapse and cocaine-enhanced nucleus accumbens dopamine in rats

Gabapentin is a gamma-aminobutyric acid (GABA) analogue, with GABAmimetic pharmacological properties. Gabapentin is used for the treatment of seizures, anxiety and neuropathic pain. It has been proposed that gabapentin may be useful in the treatment of cocaine dependence. However, clinical trials with gabapentin have shown conflicting results, while preclinical studies are sparse. In the present study, we investigated the effects of gabapentin on intravenous cocaine self-administration and cocaine-triggered reinstatement of drug-seeking behavior, as well as on cocaine-enhanced dopamine (DA) in the nucleus accumbens (NAc). We found that gabapentin (25-200mg/kg, i.p., 30min or 2h prior to cocaine) failed to inhibit intravenous cocaine (0.5mg/kg/infusion) self-administration under a fixed-ratio reinforcement schedule or cocaine-triggered reinstatement of cocaine-seeking behavior. In vivo microdialysis showed that the same doses of gabapentin produced a modest increase ( approximately 50%, p<0.05) in extracellular NAc GABA levels, but failed to alter either basal or cocaine-enhanced NAc DA. These data suggest that gabapentin is a weak GABA-mimic drug. At the doses tested, it has no effect in the addiction-related animal behavioral models here tested. This is in striking contrast to positive findings in the same animal models shown by another GABAmimetic - gamma-vinyl GABA (see companion piece to present article).     

Gabapentin-induced neurologic toxicities

Gabapentin is an antiepileptic drug approved for the treatment of postherpetic neuralgia and as adjunctive therapy for partial seizures. The drug has been shown to be safe and nontoxic. The current literature has limited reports of neurologic toxicity associated with gabapentin therapy in patients with or without renal dysfunction. We describe the case of a 75-year-old man with renal dysfunction who developed neurologic toxicity due to gabapentin accumulation. Future studies are warranted to confirm the neurologic adverse effects of gabapentin, including any additional risks in patients with renal dysfunction.     

Gabapentin as a potential option for treatment of sciatica

Gabapentin has been approved in the United States for the treatment of epilepsy and postherpetic neuralgia. Gabapentin has also demonstrated proven efficacy for the treatment of diabetic peripheral neuropathy and trigeminal neuralgia, although these represent off-label uses of the drug. However, to our knowledge, no data have been published regarding the efficacy of gabapentin for treating sciatica. We describe two patients with sciatica who were successfully treated with gabapentin. The first was a 32-year-old man with severe shooting pain in his left leg that was later diagnosed as sciatica secondary to a fifth lumbar-first sacral intervertebral disk herniation. The patient was treated with acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), narcotics, and muscle relaxants; he reported only limited pain relief with any of these agents or combination of agents. He was then prescribed gabapentin 300 mg once/day; his pain substantially improved, even after the first dose. The drug was titrated gradually up to 900 mg 3 times/day with good results. The patient subsequently underwent a laminectomy and diskectomy on the advice of his neurosurgeon, who assured him that the result would be immediate pain relief. After surgery, the patient continued to experience pain; however, his pain resolved completely after several weeks of receiving gabapentin 600 mg 3 times/day. The second patient was a 68-year-old Caucasian woman with renal insufficiency who experienced severe burning pain and numbness of abrupt onset in the posterior right leg; this was diagnosed as sciatica. The patient had contraindications for NSAID therapy and was intolerant of hydrocodone. Initial therapy with propoxyphene and acetaminophen, self-started by the patient, was ineffective. Gabapentin 100 mg at bedtime was started and then titrated up to 100 mg twice/day with 200 mg at bedtime. The patient's pain improved rapidly, and at follow-up approximately 5 weeks later, she was experiencing good pain control with gabapentin. Gabapentin is widely prescribed for management of peripheral neuropathic pain syndromes. To our knowledge, however, these two case reports are the first to describe sciatica successfully controlled with gabapentin. Because gabapentin has the potential to prevent central sensitization, consideration should be given to prescribing this therapy early in the course of sciatica. Further research using randomized, placebo-controlled trials are needed to validate the benefit of gabapentin in the treatment of sciatica.     

Gabapentin: new indication. Little impact on partial epilepsy in children between 3 and 12

(1) The standard treatment for partial epilepsy in children is carbamazepine. The efficacy of other antiepileptics has also been documented, either alone (phenobarbital, oxcarbazepine, valproate sodium, phenytoin), or in drug combinations (lamotrigine, topiramate). (2) A licence extension has been granted in France for gabapentin in partial epilepsy in children aged 3 to 12 years, in combination with other antiepileptics. (3) The clinical file contains no data from trials comparing gabapentin with other antiepileptics. (4) The main double-blind trial involved 247 children who were treated either with their usual treatment + gabapentin or usual treatment + placebo. Gabapentin was only moderately effective, and the overall number of responders did not differ significantly between the gabapentin and placebo groups. (5) In this trial the main adverse effects among the children on their usual treatment + gabapentin were behavioural disorders (hostility and mood swings). (6) In practice, the licensing of gabapentin for children with partial epilepsy aged between 3 and 12 years changes nothing in their practical management.     

Gabapentin does not affect antipyrine clearance.

The effect of gabapentin on antipyrine clearance was assessed in 12 healthy male volunteers, using a known enzyme inducer, phenytoin, as control. Subjects received gabapentin 400 mg or phenytoin 100 mg three times daily for 2 weeks. Antipyrine tests were performed before, during, and after treatment with gabapentin or phenytoin. In contrast to phenytoin, chronic administration of gabapentin did not affect antipyrine clearance. Gabapentin appears to have little potential for drug interactions.     

Gabapentin monotherapy: new indication. Sometimes helpful

(1) Gabapentin is now licensed for first-line or replacement monotherapy of partial epilepsy, in patients over 12 years of age. (2) The assessment file concurs with current recommendations of medicines agencies. (3) One comparative trial of first-line monotherapy showed a similar efficacy/adverse effects ratio of gabapentin and carbamazepine. Gabapentin has not been compared with valproate sodium. (4) In one trial, involving patients with refractory epilepsy, various doses of gabapentin were added to an ongoing inadequately effective treatment, which was then gradually stopped. Gabapentin monotherapy was considered satisfactory in a minority of patients. (5) The adverse effects of gabapentin are limited to neuropsychological disorders, namely dizzy spells, drowsiness, fatigue and headache. The risk of interactions is also limited. (6) The optimal dose regimen of gabapentin is not yet established.