A potentially hazardous interaction between erythromycin and midazolam.
A potentially hazardous interaction between erythromycin and midazolam.
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红霉素和咪达唑仑之间存在潜在危险的相互作用。
DOI：
10.1097/00132586-199312000-00005
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发表时间：
1993
影响因子：
6.7
通讯作者：
P. Neuvonen
中科院分区：
文献类型：
--
作者：
K. Olkkola;K. Aranko;H. Luurila;A. Hiller;L. Saarnivaara;J. Himberg;P. Neuvonen
红霉素和咪达唑仑之间的相互作用是在两个双盲、随机、交叉研究中进行的。在第一项研究中，12名健康志愿者每天三次服用500毫克红霉素，或服用安慰剂，为期一周。第六天，受试者摄入15毫克咪达唑仑。在第二项研究中，6名相同的受试者在接受类似的预处理后，静脉注射咪达唑仑(0.05 mg/kg)。采集血浆样本，测定精神运动能力。红霉素使口服咪达唑仑的药物浓度-时间曲线下面积增加4倍以上(p<；0.001)，静脉给药的清除量减少54%(p<；0.05)。在精神运动测试(例如眼球跳动)中，从15分钟到6小时，红霉素和口服咪达唑仑之间的相互作用具有统计学意义(p<；0.05)。红霉素和咪达唑仑通过相同的细胞色素P450IIIA同工酶代谢，可以解释观察到的药代动力学相互作用。接受红霉素治疗的患者应避免使用咪达唑仑，或将咪达唑仑的用量减少50%至75%。
Interaction between erythromycin and midazolam was investigated in two double-blind, randomized, crossover studies. In the first study, 12 healthy volunteers were given 500 mg erythromycin three times a day or placebo for 1 week. On the sixth day, the subjects ingested 15 mg midazolam. In the second study, midazolam (0.05 mg/kg) was given intravenously to six of the same subjects, after similar pretreatments. Plasma samples were collected, and psychomotor performance was measured. Erythromycin increased the area under the midazolam concentration-time curve after oral intake more than four times (p < 0.001) and reduced clearance of intravenously administered midazolam by 54% (p < 0.05). In psychomotor tests (e.g., saccadic eye movements), the interaction between erythromycin and orally administered midazolam was statistically significant (p < 0.05) from 15 minutes to 6 hours. Metabolism of both erythromycin and midazolam by the same cytochrome P450IIIA isozyme may explain the observed pharmacokinetic interaction. Prescription of midazolam for patients receiving erythromycin should be avoided or the dose of midazolam should be reduced by 50% to 75%.