Wilson E A, Sills G J, Forrest G, Brodie M J
University Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK.
Epilepsy Res. 1998 Jan;29(2):161-6. doi: 10.1016/s0920-1211(97)00078-8.
Fifty patients with refractory partial seizures took part in a prospective, observational study of adjuvant gabapentin (GBP) in increasing doses. Thirty-three were started on 400 mg GBP daily with further weekly increments of 400 mg until seizures came under control for at least 6 months or to the limit of tolerability. A further 17 patients, not fully controlled on low dose GBP, followed the same regimen. All patients took the drug three times daily. Comparisons were made with seizure numbers during a 3-month baseline during which antiepileptic medication remained unchanged. Overall, 24 of the 50 patients documented a seizure reduction of 50% or more. Fifteen did so at or below 2400 mg GBP daily. Three of these patients became seizure-free. The remaining nine appeared to respond to higher daily doses of GBP (1:2800 mg; 3:3600 mg; 1:4000 mg; 1:4800 mg; 3:6000 mg), with two becoming seizure-free. Side-effects most commonly reported included tiredness, dizziness, headache and diplopia. On GBP doses exceeding 3600 mg daily, three patients developed flatulence and diarrhoea and two more had myoclonic jerks. Mean circulating GBP concentrations (mg/l) at each 1200 mg dose level were as follows: 1200 mg-4.1; 2400 mg-8.6; 3600 mg 13.2; 4800 mg 15.5; 6000 mg-17.2. In six patients, including three taking 6000 mg daily, GBP concentrations continued to rise linearly at each dosage increment. Although limited, our results do not support the suggestion that GBP absorption is saturable. High dose GBP may be effective in controlling seizures in patients with refractory partial epilepsy.
50例难治性部分性癫痫患者参与了一项加巴喷丁（GBP）递增剂量的前瞻性观察研究。33例患者起始剂量为每日400mg GBP，之后每周增加400mg，直至癫痫发作得到控制至少6个月或达到耐受极限。另外17例低剂量GBP治疗未完全控制的患者，遵循相同方案。所有患者每日服药3次。将其与抗癫痫药物不变的3个月基线期内的癫痫发作次数进行比较。总体而言，50例患者中有24例记录癫痫发作减少50%或更多。15例在每日2400mg及以下剂量时达到这一效果。其中3例患者癫痫发作停止。其余9例患者似乎对更高的每日GBP剂量有反应（1例：2800mg；3例：3600mg；1例：4000mg；1例：4800mg；3例：6000mg），2例癫痫发作停止。最常报告的副作用包括疲倦、头晕、头痛和复视。在每日GBP剂量超过3600mg时，3例患者出现肠胃胀气和腹泻，另外2例出现肌阵挛性抽搐。每个1200mg剂量水平的平均循环GBP浓度（mg/l）如下：1200mg - 4.1；2400mg - 8.6；3600mg - 13.2；4800mg - 15.5；6000mg - 17.2。在包括3例每日服用6000mg的6例患者中，GBP浓度在每次剂量增加时持续线性上升。尽管有限，但我们的结果不支持GBP吸收饱和的观点。高剂量GBP可能对控制难治性部分性癫痫患者的癫痫发作有效。
