Tuomainen P
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Pharmacol Toxicol. 1989 Jan;64(1):28-32. doi: 10.1111/j.1600-0773.1989.tb00595.x.
In a double-blind and cross-over study 12 healthy subjects took temazepam 20 mg in two different formulations (soft gelatine capsule or uncoated tablet) and matched placebo at one-week intervals. Plasma temazepam concentrations at 0.5, 1, 2, 3, 8, 12 and 24 hours after treatment were analyzed by gas chromatography. Psychomotor performance was measured objectively (digit symbol substitution, letter cancellation, Maddox wing test) and subjectively (visual analogue scales) before the drug intake and 1, 2 and 3 hours later and the plasma benzodiazepine concentrations were analyzed also by radioreceptor bioassay. The two different formulations were compared in pharmacokinetic and pharmacodynamic terms, and the gas chromatographic and radioreceptor assays were compared. The soft gelatine capsule produced higher peak plasma concentrations than the uncoated tablet. The computed AUCs and elimination half-lives proved to be similar after either formulation. A satisfactory correlation between the bioassayed benzodiazepine concentrations and chemically assayed temazepam was shown. In pharmacodynamic terms the results suggest a shorter and somewhat smaller subjective response for the capsule than for the tablet form.
在一项双盲交叉研究中，12名健康受试者每隔一周服用20毫克替马西泮的两种不同剂型（软胶囊或未包衣片剂）及匹配的安慰剂。治疗后0.5、1、2、3、8、12和24小时的血浆替马西泮浓度通过气相色谱法进行分析。在服药前以及服药后1、2和3小时，对精神运动表现进行客观测量（数字符号替换、字母划消、马多克斯翼试验）和主观测量（视觉模拟量表），并通过放射受体生物测定法分析血浆苯二氮䓬浓度。对两种不同剂型在药代动力学和药效学方面进行比较，并对气相色谱法和放射受体测定法进行比较。软胶囊产生的血浆峰浓度高于未包衣片剂。两种剂型后的计算AUC和消除半衰期相似。生物测定的苯二氮䓬浓度与化学测定的替马西泮之间显示出良好的相关性。在药效学方面，结果表明与片剂相比，胶囊的主观反应时间更短且程度稍小。
