Verebely K, Kutt H
Res Commun Chem Pathol Pharmacol. 1975 Jul;11(3):373-86.
The stability of methadone plasma levels during steady drug intake and the effects of a single dose omission on the methadone plasma level, were studied in 3 reliable patients (Group I) and in a nonselected group of 11 clinic patients (Group II). The plasma levels of methadone were determined by gas-liquid chromatography. In Group I patients receiving an average dose of 1.13 mg/kg (range 0.45-1.6 mg/kg) little day to day variation was seen: the average plasma level was 0.358 ug/ml with a variance of +/- 3.6% measured in 4 different days. Forty-eight hours after the last dose (after omission of a single dose), methadone plasma levels declined on the average by 0.179 ug/ml which represents a 50% decrease form the preomission average level. In Group II patients during the presumed steady methadone intake (average dose 1.25 mg/kg, range 0.57-1.75 mg/kg), the average plasma level of methadone was 0.377 ug/ml with a variance of 48.5% measured in 4 different days. A fall in methadone plasma levels occurred mainly after weekends in some of the Group II patients suggesting possibly nonconsumption of the prescribed dose of medication. The rapid and substantial decline of methadone plasma levels following a single dose omission is apparently a parallel to the observed rapid loss of methadone induced cross tolerance.
在3例可靠的患者（I组）和11例门诊非选定患者（II组）中，研究了稳定药物摄入期间美沙酮血浆水平的稳定性以及单次漏服剂量对美沙酮血浆水平的影响。美沙酮的血浆水平通过气液色谱法测定。I组患者平均剂量为1.13 mg/kg（范围0.45 - 1.6 mg/kg），每日变化很小：在4个不同日期测得的平均血浆水平为0.358μg/ml，方差为±3.6%。最后一剂后48小时（单次漏服后），美沙酮血浆水平平均下降0.179μg/ml，这代表比漏服前平均水平降低了50%。在II组患者假定的美沙酮稳定摄入期间（平均剂量1.25 mg/kg，范围0.57 - 1.75 mg/kg），美沙酮的平均血浆水平为0.377μg/ml，在4个不同日期测得的方差为48.5%。II组部分患者的美沙酮血浆水平下降主要发生在周末之后，提示可能未服用规定剂量的药物。单次漏服剂量后美沙酮血浆水平的快速大幅下降显然与观察到的美沙酮诱导的交叉耐受性快速丧失相平行。
