Mutch R S, Hutson P R
University of Wisconsin Hospital and Clinics, Madison.
Clin Pharm. 1991 Feb;10(2):95-109.
The chemistry, pharmacology, pharmacokinetics, assay methodologies, adverse effects, and dosage of levamisole are described, and the clinical studies of levamisole therapy in patients with colorectal carcinoma are reviewed. Levamisole is a synthetic, orally active agent that has antihelmintic and immunomodulatory properties. It is capable of inducing T-cell differentiation and restoring depressed effector functions of peripheral lymphocytes and phagocytes to normal. The drug is well absorbed from the gastrointestinal tract after oral administration and is extensively metabolized by the liver. Gas chromatography and high-performance liquid chromatography are the most common methods used to measure concentrations of levamisole in biologic fluids. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with surgically resected Dukes stage C colon cancer; this combination is now recommended as standard therapy in these patients. Uses in patients with rectal carcinoma, Dukes stage B colon cancer, metastatic colon cancer, other malignancies, or nonmalignant disorders remain investigational. Common adverse effects include nausea, abdominal pain, vomiting, diarrhea, metallic or altered taste, flulike symptoms, mood elevation, insomnia, hyperalertness, dizziness, and headache. The most serious adverse effect associated with levamisole is granulocytopenia. The FDA-approved dosage of levamisole is 50 mg orally every eight hours for three days every two weeks. Levamisole therapy is to be initiated no earlier than 7 and no later than 30 days after surgery and is to be continued for one year. Levamisole combined with fluorouracil has been associated with a one-third reduction in recurrence and risk of death in patients with resected stage C colon cancer. Further research is needed to more clearly define the mechanism of action, optimum dose and scheduling, and clinical efficacy of levamisole in treating other malignancies.
本文描述了左旋咪唑的化学性质、药理学、药代动力学、检测方法、不良反应及剂量，并综述了左旋咪唑治疗结直肠癌患者的临床研究。左旋咪唑是一种具有驱虫和免疫调节特性的合成口服活性药物。它能够诱导T细胞分化，并使外周淋巴细胞和吞噬细胞的效应功能恢复正常。该药物口服后可从胃肠道良好吸收，并在肝脏中广泛代谢。气相色谱法和高效液相色谱法是测量生物体液中左旋咪唑浓度最常用的方法。左旋咪唑联合氟尿嘧啶可使接受手术切除的Dukes C期结肠癌患者的复发率和死亡风险降低三分之一；目前推荐该联合用药方案作为这些患者的标准治疗方法。在直肠癌、Dukes B期结肠癌、转移性结肠癌、其他恶性肿瘤或非恶性疾病患者中的应用仍在研究中。常见的不良反应包括恶心、腹痛、呕吐、腹泻、金属味或味觉改变、流感样症状、情绪高涨、失眠、过度警觉、头晕和头痛。与左旋咪唑相关的最严重不良反应是粒细胞减少症。美国食品药品监督管理局（FDA）批准的左旋咪唑剂量为每八小时口服50毫克，每两周服用三天。左旋咪唑治疗应在手术后不早于7天且不晚于30天开始，并持续一年。左旋咪唑联合氟尿嘧啶可使切除的C期结肠癌患者的复发率和死亡风险降低三分之一。需要进一步研究以更明确地确定左旋咪唑治疗其他恶性肿瘤的作用机制、最佳剂量和给药方案以及临床疗效。
