Yu D K, Dimmitt D C, Lanman R C, Giesing D H
J Pharm Sci. 1986 Jun;75(6):582-5. doi: 10.1002/jps.2600750612.
Dothiepin hydrochloride (N,N-dimethyldibenzo[b,e]thiepin-delta 11(6 H), gamma-propylamine hydrochloride) is a tricyclic antidepressant which is structurally similar to amitriptyline. Twenty-seven healthy men received three single oral doses of 50-, 100-, and 150-mg dothiepin hydrochloride capsules in a three-way randomized, crossover dose-proportionality study. Plasma concentration-time profiles of dothiepin (1) were described by both one- and two-compartment models with first-order absorption. The total intrinsic clearance of dothiepin decreased from 165.5 to 121.1 L/h as the dose was increased from 50 to 150 mg, but there was no significant effect on the terminal half-life (approximately 20 h). Plasma concentration-time profiles of the three major metabolites of dothiepin, the S-oxide derivative of dothiepin, N,N-dimethyl[b,e]thiepin-delta 11(6 H), gamma-propylamine 5-oxide (2), the demethyl derivative, N-methyldibenzo[b,e]thiepin-delta 11(6 H), gamma-propylamine (3) and the demethyl S-oxide derivative N-methyldibenzo[b,e]thiepin-delta 11(6 H), gamma-propylamine 5-oxide (4), were described by a one-compartment model with apparent first-order formation. The AUC infinity values of the S-oxide 2 and the demethyl S-oxide 4 increased proportionally with dose. The dose proportionality of the demethyl metabolite 3 may not be ascertained from the data in this study. The corresponding half-lives of the three metabolites, which are dose independent, were approximately 24, 28, and 40 h, respectively.
盐酸多塞平（N,N - 二甲基二苯并[b,e]硫杂卓 - δ¹¹(6H)，γ - 丙胺盐酸盐）是一种三环类抗抑郁药，其结构与阿米替林相似。在一项三向随机、交叉剂量比例研究中，27名健康男性接受了三剂单次口服的50毫克、100毫克和150毫克盐酸多塞平胶囊。多塞平（1）的血浆浓度 - 时间曲线用具有一级吸收的一室和二室模型描述。随着剂量从50毫克增加到150毫克，多塞平的总内在清除率从165.5升/小时降至121.1升/小时，但对末端半衰期（约20小时）没有显著影响。多塞平的三种主要代谢物的血浆浓度 - 时间曲线，即多塞平的S - 氧化物衍生物N,N - 二甲基[b,e]硫杂卓 - δ¹¹(6H)，γ - 丙胺5 - 氧化物（2）、去甲基衍生物N - 甲基二苯并[b,e]硫杂卓 - δ¹¹(6H)，γ - 丙胺（3）和去甲基S - 氧化物衍生物N - 甲基二苯并[b,e]硫杂卓 - δ¹¹(6H)，γ - 丙胺5 - 氧化物（4），用具有表观一级形成的一室模型描述。S - 氧化物2和去甲基S - 氧化物4的AUC∞值随剂量成比例增加。本研究的数据无法确定去甲基代谢物3的剂量比例关系。三种代谢物相应的半衰期与剂量无关，分别约为24小时、28小时和40小时。
