Brasseur P
UR 77, IRD, Dakar, Sénégal.
Med Trop (Mars). 2007 Jun;67(3):288-90.
Amodiaquin is still considered as a poorly tolerated antimalarial causing hematological and hepatic toxicity. In view of complications observed during prophylaxis, the WHO has advised against the use of amodiaquin for prophylaxis as well as treatment. However due to the rapid increase in chloroquine resistance and to the absence of reported cases of toxicity during treatment, the WHO has reconsidered its position and now accepts therapeutic use of amodiaquin under some conditions. It has been demonstrated that amodiaquin activates release of quinoneimine granulocytes causing hematological toxicity. In liver microsomes, metabolism into desethyl derivatives is catalyzed by cytochrome P450 CYP2C8 that has several variant forms with low activity on amodiaquin clearance. Carriers of these variants are at a higher risk for adverse effects. Currently the safety and effectiveness of amodiaquin in association with artesunate has been documented and this therapeutic combination is now recommended for first line treatment of uncomplicated Plasmodium falciparum malaria in 18 African countries.
氨酚喹仍被认为是一种耐受性较差的抗疟药，会导致血液学和肝脏毒性。鉴于在预防过程中观察到的并发症，世界卫生组织已建议不要将氨酚喹用于预防和治疗。然而，由于氯喹耐药性迅速增加，且在治疗期间未报告毒性病例，世界卫生组织重新考虑了其立场，现在在某些条件下接受氨酚喹的治疗用途。已证明氨酚喹会激活醌亚胺粒细胞的释放，从而导致血液学毒性。在肝微粒体中，细胞色素P450 CYP2C8催化其代谢为去乙基衍生物，该细胞色素有几种变体形式，对氨酚喹清除的活性较低。这些变体的携带者发生不良反应的风险更高。目前，氨酚喹与青蒿琥酯联合使用的安全性和有效性已有文献记载，这种治疗组合现在被推荐用于18个非洲国家单纯性恶性疟原虫疟疾的一线治疗。
