Barzaghi N, Gatti G, Manni R, Galimberti C A, Zucca C, Perucca E, Tartara A
Department of Medical Pharmacology, University of Pavia, Italy.
Eur J Drug Metab Pharmacokinet. 1991 Jan-Mar;16(1):81-7. doi: 10.1007/BF03189879.
The comparative pharmacokinetics and pharmacodynamics of single oral doses of eterobarbital (N,N'-dimethoxymethylphenobarbital, DMMP, 400 mg) and phenobarbital (200 mg) were evaluated in a double-blind study in 8 normal volunteers. Following administration of DMMP, no unchanged drug could be detected in serum. The active monomethoxymethyl metabolite (MMP) appeared rapidly in the circulation but its concentration remained generally low and declined below the limit of detection (0.5 micrograms/ml) usually before 9.5 h. Serum levels of DMMP-derived PB increased slowly and reached a peak between 24 and 48 h in most cases. One subject showed an atypical pharmacokinetic profile, characterized by relatively high levels of MMP and a delayed appearance of low levels of PB. After administration of PB, serum drug levels peaked within 1.5 h and remained, at all sampling times, higher than those observed after intake of DMMP. Compared with DMMP, PB induced greater sedative effects as assessed by visual analogue rating scale, critical flicker fusion frequency and multiple sleep latency tests.
在一项针对8名正常志愿者的双盲研究中，评估了单次口服400毫克埃托巴比妥（N,N'-二甲氧基甲基苯巴比妥，DMMP）和200毫克苯巴比妥的比较药代动力学和药效学。服用DMMP后，血清中未检测到未变化的药物。活性单甲氧基甲基代谢物（MMP）迅速出现在循环中，但其浓度通常保持在较低水平，通常在9.5小时之前降至检测限（0.5微克/毫升）以下。DMMP衍生的PB血清水平缓慢上升，大多数情况下在24至48小时之间达到峰值。一名受试者表现出非典型的药代动力学特征，其特点是MMP水平相对较高，PB水平较低且出现延迟。服用PB后，血清药物水平在1.5小时内达到峰值，在所有采样时间均高于服用DMMP后观察到的水平。通过视觉模拟评分量表、临界闪烁融合频率和多次睡眠潜伏期测试评估，与DMMP相比，PB诱导的镇静作用更强。
