Mercadante S, Sapio M, Serretta R, Caligara M
Pain Relief and Palliative Care, SAMOT, Palermo, Italy.
Ann Oncol. 1996 Aug;7(6):613-7. doi: 10.1093/oxfordjournals.annonc.a010679.
Methadone is a very useful drug in cancer pain because of its low cost, lack of active metabolites, high oral availability, and the rapid onset of its analgesic effect. It seems to be well tolerated in patients with difficult pain syndromes who are receiving high doses of opioids, and it may deter the development of tolerance, but a high individual variation in terminal elimination half-life can result in different rates and extents of drug accumulation. For this reason, oral patient-controlled analgesia with methadone was used in 24 advanced-disease patients with pain.
A regimen of self-administered oral methadone at fixed doses and flexible patient-controlled dosage intervals to achieve adequate analgesia, while avoiding toxic effects of methadone accumulation, was used in 24 patients requiring opioid therapy. After a priming period of three days with fixed doses of 3-5 mg three times a day for naïve patients and 50% of the morphine equivalent of methadone in patients switched from morphine, patients and relatives were instructed to maintain the night-time dose and to administer a second dose when the pain recurred. When more than four doses of methadone a day were used, an increase of the dosage was prescribed. Continuous pain assessment and monitoring of symptoms were offered.
The majority of patients achieved good pain relief until death, and three were switched to very low doses of subcutaneous morphine in their final days. The methadone escalation index was about 2% a day, with a mean dosage increase of 0.3 mg a day for an average of 60 days of treatment at doses ranging from 9 to 80 mg. The plasma concentration in 14 patients ranged from 0.013 to 0.273 mcg/ml with dosages of 20-80 mg during chronic treatment. A mean of 2.4 doses a day was reported, including the fixed night-time dose. The extent of side effects was considered acceptable.
Patient-administered analgesia with oral methadone appears to be a simple, cheap and relatively safe technique for controlling cancer pain, permitting individualization by the patient him- or herself and avoiding the risk of accumulation. Continuous assessment is necessary.
美沙酮是一种在癌症疼痛治疗中非常有用的药物，因其成本低、无活性代谢产物、口服生物利用度高且镇痛作用起效迅速。对于接受高剂量阿片类药物治疗且疼痛综合征复杂的患者，美沙酮似乎耐受性良好，并且可能延缓耐受性的产生，但其终末消除半衰期存在较大个体差异，这可能导致药物蓄积的速率和程度不同。因此，对24例晚期疼痛患者采用了美沙酮口服患者自控镇痛法。
对24例需要阿片类药物治疗的患者，采用固定剂量和灵活的患者自控给药间隔时间的口服美沙酮方案来实现充分镇痛，同时避免美沙酮蓄积的毒性作用。对于初次使用的患者，给予为期三天的初始剂量治疗，每天三次，每次3 - 5毫克；对于从吗啡转换过来的患者，给予美沙酮吗啡当量的50%。之后，指导患者及其家属维持夜间剂量，并在疼痛复发时给予第二剂。当每天使用美沙酮超过四剂时，增加剂量。同时提供持续的疼痛评估和症状监测。
大多数患者直至死亡时疼痛得到了良好缓解，有三例在临终前改用了极低剂量的皮下注射吗啡。美沙酮剂量递增指数约为每天2%，在9至80毫克的剂量范围内平均治疗约60天，每天平均剂量增加0.3毫克。14例患者在慢性治疗期间剂量为20 - 80毫克时，血浆浓度范围为0.013至0.273微克/毫升。据报告，包括固定的夜间剂量在内，平均每天给药2.4剂。副作用程度被认为是可接受的。
口服美沙酮患者自控镇痛似乎是一种简单、廉价且相对安全的控制癌症疼痛的技术，允许患者自行个体化给药并避免蓄积风险。持续评估是必要的。
