Tansella M, Zimmermann Tansella C, Ferrario L, Preziati L, Tognoni G, Lader M
Pharmakopsychiatr Neuropsychopharmakol. 1978 Mar;11(2):68-75. doi: 10.1055/s-0028-1094564.
Twenty-four anxious inpatients were treated with diazepam, amylobarbitone and placebo, each given in flexible dosage for one week, according to a fully-balanced design. Plasma concentrations of diazepam and of its metabolite nordiazepam and of amylobarbitone were determined after two, four and seven days of treatment. Clinical and psychological assessments were made after seven days of each treatment by means of psychiatrist rating scales, patient's self-rating and a comprehensive battery of performance measures. Diazepam and nordiazepam but not amylobarbitone were accumulating over the seven days of treatment. In patients on diazepam without previous amylobarbitone, nordiazepam accumulated more rapidly than diazepam over the week so that the ratio of diazepam to nordiazepam was 2.21 after two days but only 1.14 after seven days; those with previous amylobarbitone on the other hand always had nordiazepam concentrations higher than those of the administered drug and both were accumulating equally. Diazepam and nordiazepam were still detectable in most patients two weeks after the interruption of treatment. No correlations were found between drug concentrations and clinical and psychological effects.
24名焦虑的住院患者接受了地西泮、异戊巴比妥和安慰剂治疗,根据完全平衡设计,每种药物以灵活剂量给药一周。在治疗的第2天、第4天和第7天后测定地西泮及其代谢产物去甲地西泮以及异戊巴比妥的血浆浓度。在每种治疗7天后,通过精神科医生评定量表、患者自评以及一系列综合的性能指标进行临床和心理评估。在治疗的7天中,地西泮和去甲地西泮在体内蓄积,而异戊巴比妥则没有。在未服用过异戊巴比妥的患者中,服用地西泮时,去甲地西泮在一周内的蓄积速度比地西泮更快,因此地西泮与去甲地西泮的比值在第2天后为2.21,但在第7天后仅为1.14;另一方面,之前服用过异戊巴比妥的患者,其去甲地西泮浓度始终高于给药药物浓度,且两者蓄积速度相同。在治疗中断两周后,大多数患者体内仍可检测到地西泮和去甲地西泮。未发现药物浓度与临床及心理效应之间存在相关性。