Singh Devada, Kennedy Deborah H
Pharmacy Practice, Nova Southeastern University College of Pharmacy-Davie Campus, Fort Lauderdale, Florida 33328-2018, USA.
Clin Ther. 2003 Mar;25(3):852-89. doi: 10.1016/s0149-2918(03)80111-x.
Varicella-zoster virus causes chickenpox and can reemerge later in life to cause herpes zoster or shingles. One of the most common and disabling complications of herpes zoster is postherpetic neuralgia (PHN).
This article reviews the current primary literature about the efficacy and tolerability of gabapentin for the treatment of PHN. Gabapentin pharmacokinetics and drug interactions are also reviewed.
A literature search in the English language was conducted using OVID Web, which contained the following databases: MEDLINE (1966-present), EMBASE (1980-2002), Current Contents/Clinical Medicine (1999-2002), Cochrane Controlled Trials Register (1898-present), Cochrane Database of Systemic Reviews (fourth quarter, 2002), and International Pharmaceutical Abstracts (1970-2002). Search terms used were postherpetic neuralgia; zoster; gabapentin; neuropathic pain; pain; pharmacoeconomic; cost; controlled clinical trial; randomized, controlled trial; postherpetic neuralgia and gabapentin; gabapentin and pain; treatment and postherpetic neuralgia; gabapentin and age; gabapentin and gender; gabapentin and ethnicity; and gabapentin and pharmacokinetics.
Gabapentin displays nonlinear absorption kinetics, is minimally protein bound (< 3%), has a high mean (SD) volume of distribution (50.4 [8.0] L), and is excreted via the kidneys as unchanged drug. Two randomized, placebo-controlled, parallel-group, multicenter clinical trials demonstrated the effectiveness of gabapentin at doses of up to 3600 mg/d to significantly reduce pain (P < 0.01 and P < 0.001), improve sleep (P < 0.01), and improve some parameters on the Short Form-McGill Pain Questionnaire (P < 0.05). Dizziness and somnolence were the most common side effects leading to withdrawal from the trials. The recommended dosage in adults is 300 mg at bedtime on day 1,300 mg BID on day 2, and 300 mg TID on day 3, titrating up as needed to 2400 to 3600 mg/d. To reduce adverse events in patients with renal impairment, the dose should be adjusted based on the patient's creatinine clearance.
Gabapentin appears to be effective and well tolerated for the short-term treatment of PHN. However, future controlled studies are needed to determine whether the effectiveness of gabapentin for PHN is maintained for > 2 months, to establish the optimal dose of gabapentin for PHN, and to compare the efficacy of gabapentin with that of other pharmacologic agents used for the treatment of PHN.
水痘带状疱疹病毒引起水痘,且可在日后复发引发带状疱疹或称作缠腰火丹。带状疱疹最常见且致残的并发症之一是带状疱疹后神经痛(PHN)。
本文回顾了关于加巴喷丁治疗PHN的疗效和耐受性的当前主要文献。还对加巴喷丁的药代动力学和药物相互作用进行了综述。
使用OVID网络进行英文文献检索,该网络包含以下数据库:医学索引数据库(1966年至今)、荷兰医学文摘数据库(1980 - 2002年)、临床医学现刊目录(1999 - 2002年)、考克兰对照试验注册库(1898年至今)、考克兰系统评价数据库(2002年第四季度)以及国际药学文摘(1970 - 2002年)。使用的检索词为:带状疱疹后神经痛;带状疱疹;加巴喷丁;神经性疼痛;疼痛;药物经济学;成本;对照临床试验;随机对照试验;带状疱疹后神经痛与加巴喷丁;加巴喷丁与疼痛;治疗与带状疱疹后神经痛;加巴喷丁与年龄;加巴喷丁与性别;加巴喷丁与种族;以及加巴喷丁与药代动力学。
加巴喷丁呈现非线性吸收动力学,蛋白结合率极低(<3%),平均(标准差)分布容积较高(50.4 [8.0] L),且以原形药物经肾脏排泄。两项随机、安慰剂对照、平行组、多中心临床试验表明,加巴喷丁剂量高达3600 mg/d时可有效显著减轻疼痛(P < 0.01和P < 0.001)、改善睡眠(P < 0.01)并改善简短麦吉尔疼痛问卷的一些参数(P < 0.05)。头晕和嗜睡是导致试验中止的最常见副作用。成人推荐剂量为第1天睡前300 mg,第2天每日2次,每次300 mg,第3天每日3次,每次300 mg,根据需要可滴定至2400至3600 mg/d。为减少肾功能损害患者的不良事件,应根据患者的肌酐清除率调整剂量。
加巴喷丁似乎对PHN的短期治疗有效且耐受性良好。然而,需要未来的对照研究来确定加巴喷丁对PHN的有效性是否能维持超过2个月,确定PHN的加巴喷丁最佳剂量,并比较加巴喷丁与用于治疗PHN的其他药物的疗效。