Kaiko R F, Inturrisi C E
Clin Pharmacol Ther. 1975 Jul;18(1):96-103. doi: 10.1002/cpt197518196.
The levels of acetylmethadol and its active biotransformation products were quantitated in the plasma and urine of subjects on acetylmethadol maintenance by the use of solvent extraction and gas-liquid chromatography. The time-course of plasma acetylmethadol, noracetylmethadol, and dinoracetylmethadol over 48 hr was determined concurrently with the time-action of pupillary constriction in 8 subjects receiving an average oral maintenance dose of 50 mg. The plasma level of acetylmethadol reached a peak at 4 hr and had nearly disappeared by 24 hr. The mean apparent half-life was 7 hr. The plasma level of noracetylmethadol peaked at 4 to 8 hr and slowly declined over the next 40 hr. The mean apparent half-life of noracetylmethadol was 48 hr. Dinoracetylmethadol plasma levels remained relatively constant throughout the dosing interval. The miotic effect reached a peak at 8 hr and decayed at a rate slower than that of plasma elimination of acetylmethadol but more rapidly than that of noracetylmethadol and dinoracetylmethadol. Substantial variation in the plasma levels of the compounds was observed in subjects after the same doses. The study indicated that the relatively long duration of opiate effects of acetylmethadol results from biotransformation to active and persistent metabolites.
通过溶剂萃取和气液色谱法，对接受醋美沙朵维持治疗的受试者血浆和尿液中醋美沙朵及其活性生物转化产物的水平进行了定量分析。在8名平均口服维持剂量为50毫克的受试者中，同时测定了48小时内血浆中醋美沙朵、去乙酰美沙朵和双去乙酰美沙朵的时间进程以及瞳孔收缩的时效关系。醋美沙朵的血浆水平在4小时达到峰值，到24小时时几乎消失。平均表观半衰期为7小时。去乙酰美沙朵的血浆水平在4至8小时达到峰值，并在接下来的40小时内缓慢下降。去乙酰美沙朵的平均表观半衰期为48小时。在整个给药间隔期间，双去乙酰美沙朵的血浆水平保持相对恒定。缩瞳效应在8小时达到峰值，其衰减速度比醋美沙朵的血浆消除速度慢，但比去乙酰美沙朵和双去乙酰美沙朵快。相同剂量给药后，受试者体内这些化合物的血浆水平存在显著差异。该研究表明，醋美沙朵的阿片类效应持续时间相对较长是由其生物转化为活性和持久性代谢产物所致。
