Rimantadine: A Clinical Perspective
Rimantadine: A Clinical Perspective
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DOI：
10.1177/106002809502900312
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发表时间：
1995-03
影响因子：
2.9
通讯作者：
S. M. Wintermeyer;M. Nahata
中科院分区：
文献类型：
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作者：
S. M. Wintermeyer;M. Nahata
目的：综述金刚乙胺的抗病毒活性、药代动力学、疗效、不良反应、药物相互作用、剂量和用法。介绍有关甲型流感病毒和流感疾病的临床特征的信息。描述了金刚乙胺和金刚烷胺的比较数据。资料来源：应用计算机检索MEDLINE 1966~1994年间发表的英文文献，并对期刊进行广泛的综述。资料提炼：从开放和对照研究中有关金刚乙胺的各种文章中获得有关抗病毒活性、药代动力学、不良反应和药物相互作用的数据。对金刚乙胺预防和治疗甲型流感感染的疗效进行双盲对照研究。资料综合：在健康成人中，超过90%的金刚乙胺在3-6小时内被吸收。婴儿每天3 mg/kg剂量的稳态血药浓度为0.1~2.60μg/m L，老年人为100 mg/d，每日两次。金刚乙胺在稳态时的鼻液浓度是血浆浓度的1.5倍，这可能解释了金刚乙胺在低血浆浓度下的有效性。超过75%的金刚乙胺在肝脏中代谢，母体化合物和代谢物几乎完全被肾脏消除。消除半衰期从24.8到36.5小时，允许每天给药一次。建议对有严重肾损害(肌酐清除量≤为0.17毫升/S)、严重肝功能障碍的患者或养老院老年患者进行剂量调整。在几项针对儿童和/或成人的研究中，出现了对金刚乙胺具有抗药性的甲型流感病毒株。耐药菌株的临床意义尚未确定。金刚乙胺预防甲型流感的有效率为85%-90%，预防甲型流感感染的有效率为50%-65%。与安慰剂相比，金刚乙胺将症状减少50%的时间缩短了1-3天。金刚乙胺和安慰剂在治疗前3天的症状缓解方面的差异通常在临床上没有显著意义。金刚乙胺最常见的不良反应与中枢神经系统(CNS)和胃肠道(GI)有关。10岁以下儿童和成人中与中枢神经系统相关的不良反应发生率分别为3.2%和8.4%。老年患者中枢神经系统相关不良反应发生率为4.9%~12.5%，10岁以下儿童发生率为8.4%，成人为3.1%，100 mg/d和200 mg/d分别为2.9%和17.0%。结论：金刚乙胺为甲型流感的治疗和预防提供了一些理想的特征。对于有金刚烷胺不良反应的老年患者和有轻度或中度肾损害的患者来说，它似乎是一个有吸引力的选择。尽管金刚乙胺被批准每天服用两次，但它的药代动力学特征允许每天服用一次。它对预防(而不是暴露后预防)和治疗甲型流感病毒有效。它的不良反应发生率也很低。
Objective: To provide a review of rimantadine, including its antiviral activity, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage and administration. Information on influenza A virus and clinical features of influenza disease are presented. Comparative data on rimantadine and amantadine are described. Data Sources: A MEDLINE search restricted to English-language literature published from 1966 through 1994 and an extensive review of journals was conducted. Data Extraction: The data on antiviral activity, pharmacokinetics, adverse effects, and drug interactions were obtained from various articles on rimantadine in open and controlled studies. Controlled double-blind studies were evaluated to assess the efficacy of rimantadine in prophylaxis and treatment of influenza A infection. Data Synthesis: Over 90% of a rimantadine dose was absorbed in 3–6 hours in healthy adults. Steady-state plasma concentrations have ranged from 0.10 to 2.60 μg/mL at doses of 3 mg/kg/d in infants to 100 mg twice daily in the elderly. Nasal fluid concentrations of rimantadine at steady-state were 1.5 times higher than plasma concentrations, which may explain the effectiveness of rimantadine despite a low plasma concentration. Over 75% of a rimantadine dose was metabolized in the liver, and the parent compound and metabolites were almost completely eliminated by the kidneys. The elimination half-life ranged from 24.8 to 36.5 hours, which allows once-daily dosing. Dosage adjustment is recommended for patients with severe renal impairment (creatinine clearance ≤ 0.17 mL/s), severe hepatic dysfunction, or elderly nursing home patients. Drug-resistant strains of influenza A virus to rimantadine occurred in several studies with children and/or adults. Clinical significance of drug-resistant strains has not been established. Rimantadine appeared to be effective in 85–90% of individuals for prevention of influenza A illness and in 50–65% for prevention of influenza A infection. Rimantadine reduced the time to a 50% reduction in symptoms by 1–3 days versus placebo. Differences in symptom reduction between rimantadine and placebo after the first 3 days of treatment was not generally clinically significant. The most common adverse effects of rimantadine administration were associated with the central nervous system (CNS) and the gastrointestinal (GI) tract. CNS-related adverse effects occurred in 3.2% of children younger than 10 years of age and 8.4% of adults. In elderly patients, the incidence of CNS-related adverse effects ranged from 4.9% at 100 mg/d to 12.5% at 200 mg/d. GI adverse effects occurred in 8.4% of children younger than 10 years of age, 3.1% of adults, and 2.9% at 100 mg/d and 17.0% at 200 mg/d in the elderly. Conclusions: Rimantadine offers some desirable features for the treatment and prophylaxis of influenza A infection. It appears to be an attractive choice in elderly patients with a history of CNS adverse effects from amantadine and in patients with mild or moderate renal impairment. Although approved for twice-daily dosing, rimantadine has a pharmacokinetic profile that would allow once-daily dosing. It is effective for prophylaxis (not postexposure prophylaxis) and treatment of influenza A virus. It also has a low incidence of adverse effects.