Prophylactic amantadine dose and plasma concentration—effect relationships in healthy adults
Prophylactic amantadine dose and plasma concentration—effect relationships in healthy adults
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健康成人中预防性金刚烷胺剂量和血浆浓度的效应关系
DOI：
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发表时间：
1985
期刊：
影响因子：
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通讯作者：
R. Ogilvie
中科院分区：
文献类型：
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作者：
F. Aoki;H. Stiver;D. Sitar;A. Boudreault;R. Ogilvie
在一项双盲、安慰剂对照研究中，研究了金刚烷胺的剂量、血药浓度、预防和不良反应与健康年轻成人受试者预防甲型流感病毒感染的关系。将74例抗减毒甲型流感病毒AF 9/Montreal/3/72（H3 N2）血凝抑制抗体滴度≤16的受试者随机分配至0（安慰剂）、25、100或150 mg金刚烷胺糖浆组，每日两次，共31剂。其他18例受试者被随机分配到对照组，以研究药物毒性（150 mg）或并发其他病毒感染（安慰剂）。三种金刚烷胺剂量的稳态血浆谷浓度分别为110 ± 39、302 ± 80和572 ± 207 ng/ml（X ± SD），且增加与剂量不成比例。预防组在第5次给药后在稳态时鼻内用病毒进行攻毒;对照组受试者接受生理盐水。无受试者患病。攻毒后48或72小时，从9/21例服用安慰剂的受试者、1/18例服用100 mg金刚烷胺的受试者、3/18例服用25 mg金刚烷胺的受试者和6/17例服用150 mg金刚烷胺的受试者的鼻或咽拭子中回收输入病毒。血清转换率或不良症状无差异。我们的数据不支持改变健康年轻人中A型流感病毒感染的金刚烷胺预防剂量。我们定义了与推荐的100 mg每日两次金刚烷胺剂量相关的稳态血药谷浓度，在为具有不同金刚烷胺动力学的人群设计剂量方案时应模拟该剂量。
Amantadine dose, plasma concentration, prophylactic and adverse effect relationships for prevention of influenza A virus infection in healthy young adult subjects were investigated in a double‐blind, placebo‐controlled study. Seventy‐four subjects with hemagglutination inhibition antibody titers ≤16 against an attenuated influenza A virus AF9/Montreal/3/72 (H3N2) were randomly allocated to groups taking 0 (placebo), 25,100, or 150 mg amantadine syrup prophylactically twice a day for 31 doses. Eighteen other subjects were randomly allocated to control groups for investigation of drug toxicity (150 mg) or concurrent other virus infection (placebo). Steady‐state trough plasma concentrations were 110 ± 39, 302 ± 80, and 572 ± 207 ng/ml (X̄ ± SD) for the three amantadine doses and increased out of proportion to dose. Prophylaxis groups were challenged intranasally with virus after the fifth dose at steady state; control subjects received saline solution. No subject became ill. Input virus was recovered 48 or 72 hr after challenge from nose or throat swabs of nine of 21 subjects taking placebo, one of 18 subjects taking 100 mg amantadine, three of 18 subjects taking 25 mg amantadine, and six of 17 subjects taking 150 mg amantadine. There were no differences in seroconversion rates or adverse symptoms. Our data do not support a change in the recommended amantadine prophylactic dose for influenza A virus infection in healthy young adults. We defined trough steady‐state plasma concentrations associated with the recommended amantadine dose of 100 mg twice a day that should be mimicked in devising dose schedules for populations with differing amantadine kinetics.