DIFFERENCES IN SIDE-EFFECTS OF AMANTADINE HYDROCHLORIDE AND RIMANTADINE HYDROCHLORIDE RELATE TO DIFFERENCES IN PHARMACOKINETICS
DIFFERENCES IN SIDE-EFFECTS OF AMANTADINE HYDROCHLORIDE AND RIMANTADINE HYDROCHLORIDE RELATE TO DIFFERENCES IN PHARMACOKINETICS
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DOI：
10.1128/aac.23.3.458
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发表时间：
1983-01-01
影响因子：
4.9
通讯作者：
SPYKER, DA
中科院分区：
文献类型：
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作者：
HAYDEN, FG;HOFFMAN, HE;SPYKER, DA
在一项双盲、安慰剂对照研究中，测定了盐酸金刚烷胺和盐酸金刚乙胺的毒性和血药浓度。健康的工作成年人分次摄入200（n = 52）或300 mg（n = 196）/天，持续4.5天。首次给药后4小时，接受100 mg（金刚乙胺和金刚烷胺分别为140 ng/ml和300 ng/ml; P < 10-5）或200 mg剂量（310 ng/ml和633 ng/ml; P < 10-5）金刚乙胺的受试者的平均血浆药物浓度较低。第一次给药后的血浆药物浓度与金刚烷胺和金刚乙胺的总症状来源显著相关;中毒和非中毒受试者的血浆水平广泛重叠。在300 mg/天剂量下，金刚烷胺更常与CNS不良症状（金刚烷胺组33%对金刚乙胺组9%; P < 0.001）和睡眠障碍（39对13%; P < 0.001）相关，但与胃肠道症状无关（19.5对16.0%）。在具有相似血浆浓度的志愿者中，未观察到药物之间的症状频率或评分差异。金刚烷胺和金刚乙胺的药代动力学不同，但在相似的血浆浓度下，它们的潜在副作用没有差异。
In a double-blind, placebo-controlled study, the comparative toxicities and blood concentrations of amantadine hydrochloride and rimantadine hydrochloride were determined. Healthy, working adults ingested 200 (n = 52) or 300 mg (n = 196)/day in divided doses for 4.5 days. Mean plasma drug concentrations at 4 h after the 1st dose were lower in rimantadine recipients given 100- (140 vs. 300 ng/ml for rimantadine and amantadine, respectively; P < 10-5) or 200-mg doses (310 vs. 633 ng/ml; P < 10-5). The plasma drug concentrations after the 1st dose correlated significantly with total symptom sources for amantadine and rimantadine; the plasma levels of intoxicated and non-intoxicated subjects overlapped extensively. At 300 mg/day dosage, amantadine was associated more often with adverse CNS symptoms (33% of amantadine vs. 9% of rimantadine recipients; P < 0.001) and sleep disturbance (39 vs. 13%; P < 0.001), but not gastrointestinal symptoms (19.5 vs. 16.0%). No differences between the drugs were noted in symptom frequency or scores in volunteers with similar plasma concentrations. Amantadine and rimantadine differ in their pharmacokinetics, but not in their potential for side effects at comparable plasma concentrations.