Säwe J, Hansen J, Ginman C, Hartvig P, Jakobsson P A, Nilsson M I, Rane A, Anggård E
Br Med J (Clin Res Ed). 1981 Mar 7;282(6266):771-3. doi: 10.1136/bmj.282.6266.771.
Fourteen patients with severe cancer pain participated in a trial of methadone given in a fixed dose (10 mg) but at intervals selected by the patients themselves during the loading phase. The aim was to achieve rapid pain relief while avoiding the risk of toxicity from accumulation of methadone. As expected, the dosage intervals increased gradually over the first few days of treatment, the daily dose decreasing from 30-80 mg on the first day to 10-40 mg at the end of the week. Plasma concentrations of methadone varied sevenfold after four to five days (0.24 to 1.75 mumol/1; 7.4 to 54.2 microgram/100 ml). Eleven patients reported complete or almost complete pain relief and elected to continue with methadone after the study. In no case was treatment withdrawn because of intoxication. From these findings a patient-controlled dosage regimen of oral methadone may be an effective and safe alternative to parenteral narcotic medication, adjusting both for individual variation in pain intensity and for pharmacokinetics.
14名患有重度癌痛的患者参与了一项美沙酮试验,试验中给予固定剂量(10毫克)的美沙酮,但在负荷期由患者自行选择给药间隔时间。目的是在避免美沙酮蓄积导致中毒风险的同时实现快速止痛。正如预期的那样,给药间隔时间在治疗的头几天逐渐增加,每日剂量从第一天的30 - 80毫克降至周末的10 - 40毫克。四至五天后,美沙酮的血浆浓度变化了七倍(0.24至1.75微摩尔/升;7.4至54.2微克/100毫升)。11名患者报告疼痛完全或几乎完全缓解,并在研究结束后选择继续使用美沙酮。没有一例因中毒而停止治疗。根据这些发现,口服美沙酮的患者自控给药方案可能是胃肠外麻醉药物的一种有效且安全的替代方法,可根据个体疼痛强度差异和药代动力学进行调整。