Marquer C, Trouvin J H, Lacolle J Y, Dupont C, Jacquot C
Laboratoires Debat, Garches, France.
Eur J Drug Metab Pharmacokinet. 1991 Jul-Sep;16(3):183-8. doi: 10.1007/BF03189957.
Thymoxamine, a prodrug, is rapidly deacetylated in the plasma to give two phase I metabolites, DMAT and DAT, which are further sulpho- and glucuro-conjugated and then excreted mainly in the urine. In a cross-over study, the dose-dependence of the metabolite ratio was evaluated in nine healthy volunteers after three doses (120, 240, 480 mg) of thymoxamine-HCl. Regardless of the dose, DMAT and its glucuronide were not detected, while the amount of DMAT-sulphate was found to be proportional to the dose administered. Plasma levels of DAT were measurable in only four of the nine subjects after the 480 mg dose and showed great intersubject variability. The pharmacokinetics of both DAT-sulphate and DAT-glucuronide were dose-dependent. As the dose increased, the proportion of DAT undergoing sulphatation decreased; this saturation was compensated by glucuronidation.
噻吗洛尔是一种前体药物，在血浆中迅速脱乙酰化生成两种I相代谢产物，即DMAT和DAT，它们进一步进行硫酸化和葡萄糖醛酸化，然后主要经尿液排泄。在一项交叉研究中，对9名健康志愿者服用三剂（120、240、480 mg）盐酸噻吗洛尔后的代谢产物比例的剂量依赖性进行了评估。无论剂量如何，均未检测到DMAT及其葡萄糖醛酸化物，而硫酸化DMAT的量与给药剂量成正比。在9名受试者中，仅4名在服用480 mg剂量后可测得DAT的血浆水平，且个体间差异很大。硫酸化DAT和葡萄糖醛酸化DAT的药代动力学均呈剂量依赖性。随着剂量增加，发生硫酸化的DAT比例下降；这种饱和现象通过葡萄糖醛酸化得到补偿。
