Mackenzie A H
Am J Med. 1983 Jul 18;75(1A):5-10. doi: 10.1016/0002-9343(83)91264-0.
The pharmacokinetics, physiologic effects, and the metabolization of chloroquine and hydroxychloroquine are all similar. Their concentrations in plasma and tissue are directly related to daily dosing. The highest concentrations are found in melanin-containing tissues, particularly the choroid and ciliary body of the eye. The pharmacologic effects of 4-aminoquinoline compounds are reviewed in detail. It is likely that the rheumatologic effectiveness of these agents is primarily related to lysosomal actions. The drug-induced lysosomal abnormalities include diminished vesicle fusion, diminished exocytosis, and reversible "lysosomal storage disease." It is likely that the retinal toxicity of these drugs is one manifestation of the altered lysosomal physiology involving the retinal pigmented epithelium. Tissue of retinal pigmented epithelium is similar to that of the bone-marrow-derived macrophage. Depression of extra-oculogram is an early sign of excessive dosage and can be used to measure potential toxicity during therapy with 4-aminoquinolines. Dosages ranging from 3.5 to 4.0 mg/kg per day for chloroquine and 6.0 to 6.5 mg/kg per day for hydroxychloroquine are clinically safe.
氯喹和羟氯喹的药代动力学、生理效应及代谢情况均相似。它们在血浆和组织中的浓度与每日剂量直接相关。在含黑色素的组织中浓度最高，尤其是眼部的脉络膜和睫状体。对4-氨基喹啉化合物的药理作用进行了详细综述。这些药物在风湿病治疗方面的有效性可能主要与溶酶体作用有关。药物诱导的溶酶体异常包括囊泡融合减少、胞吐作用减弱以及可逆性“溶酶体贮积病”。这些药物的视网膜毒性可能是涉及视网膜色素上皮的溶酶体生理改变的一种表现。视网膜色素上皮组织与骨髓来源的巨噬细胞组织相似。眼外肌电图降低是过量用药的早期迹象，可用于在4-氨基喹啉治疗期间测量潜在毒性。氯喹每日剂量为3.5至4.0毫克/千克、羟氯喹每日剂量为6.0至6.5毫克/千克在临床上是安全的。
