Costa Queiroz Regina Helena, de Souza Ana Maria, Sampaio Suely Vilela, Melchior Enzo
Department of Clinical, Toxicological and Food Sciences Analysis, Faculty of Pharmaceutical Sciences of São Paulo, Av.do Café s/n Monte Alegre, 14040-903 Ribeirão Preto, São Paulo, Brazil.
Pharmacol Res. 2002 Aug;46(2):191-4. doi: 10.1016/s1043-6618(02)00086-5.
Gastrointestinal toxicity and red skin discoloration were the major side effects observed in leprosy patients undergoing long-term treatment with clofazimine (CFZ). Hematological and biochemical alterations have been cited among other side effects; however, their real magnitude and clinical significance at the doses currently employed in therapy have not been sufficiently documented. We therefore investigated the correlation between CFZ plasma concentration and biochemical (transaminases, bilirubins, alkaline phosphatase, gamma-glutamyltransferase, amylase, urea, creatinine, and potassium plasma levels) as well as hematological changes blood and reticulocyte counts, osmotic fragility, detection of Heinz bodies and methemoglobinemia (MHM), following in two regimes of treatment: CFZ as a single drug and CFZ as part of multidrug (MDT) therapy, in combination with dapsone and rifampicin. MHM and hemolytic anemia were detected in the MDT group only. Eosinophilia was found in patients of either group. Determination of hepatic, pancreatic and renal biochemical parameters showed rare, occasional changes of apparently no clinical significance. We conclude that CFZ is a generally well tolerated and safe drug when given as a daily dose of 50mg, which is currently used in leprosy patients.
胃肠道毒性和皮肤发红变色是接受氯法齐明（CFZ）长期治疗的麻风病患者中观察到的主要副作用。血液学和生化改变也被列为其他副作用；然而，在目前治疗中所使用剂量下它们的实际严重程度和临床意义尚未得到充分记录。因此，我们研究了在两种治疗方案下CFZ血浆浓度与生化指标（转氨酶、胆红素、碱性磷酸酶、γ-谷氨酰转移酶、淀粉酶、尿素、肌酐和血钾水平）以及血液学变化（血细胞和网织红细胞计数、渗透脆性、Heinz小体检测和高铁血红蛋白血症（MHM））之间的相关性：CFZ单药治疗以及CFZ作为多药联合疗法（MDT）的一部分，与氨苯砜和利福平联合使用。仅在MDT组中检测到MHM和溶血性贫血。两组患者均出现嗜酸性粒细胞增多。肝、胰和肾生化参数的测定显示罕见的、偶尔的变化，显然无临床意义。我们得出结论，当每日剂量为50mg时，CFZ是一种耐受性良好且安全的药物，目前用于麻风病患者。
