Primaquine is a potent antimalarial medication indicated for the radical cure of malaria caused by and species (1, 2). Malaria is a blood borne infection caused by infection of parasites that is spread by mosquitos. The and species present a particular challenge to treat because the parasitic life cycle includes a dormant, liver-specific stage that is not susceptible to other antimalarial medications. Thus, primaquine is often used with other therapies such as chloroquine or artemisinin-based medicines that target the reproductive, active forms of the parasite. Primaquine is also used to prevent transmission of malaria caused by ( species. A single, low dose (SLD) of primaquine has gametocidal activity, which does not cure the individual but does provide malaria transmission control. Primaquine is a pro-drug that must be activated by the cytochrome P450 (CYP) enzyme system. Metabolism by the cytochrome P450 member 2D6 (CYP2D6) and cytochrome P450 nicotinamide adenine dinucleotide phosphate (NADPH):oxidoreductase (CPR) generates 2 hydroxylated active metabolites that generate hydrogen peroxide (HO). This causes significant oxidative stress to the malarial parasite and the host human cells. Individuals who are glucose-6-phosphate dehydrogenase (G6PD) deficient are particularly susceptible to oxidative stress and may experience acute hemolytic anemia (AHA). Before starting a course of primaquine, individuals should be tested for G6PD deficiency to ensure safe administration (1, 2). According to the FDA-approved drug label, individuals with severe G6PD deficiency should not take primaquine (Table 1) (1). The World Health Organization (WHO) recommends that individuals with G6PD deficiency should be treated with a modified course of primaquine therapy. The recommended course for individuals with G6PD deficiency is a single dose once per week for 8 weeks, while the standard course is daily administration for 14 days (Table 2) (2). The Clinical Pharmacogenetics Implementation Consortium (CPIC) reports that the risk of adverse effects of primaquine therapy for G6PD-deficient individuals is dose-dependent, with the SLD regimen presenting the least risk (Table 3) (3). Primaquine is contraindicated during pregnancy and is not recommended for breastfeeding individuals when the G6PD status of the baby is unknown(1, 2). Primaquine is not approved for individuals under 6 months of age. Individuals with acute illness that are prone to granulocytopenia or individuals taking another hemolytic medication are also contraindicated from taking primaquine. (1)
伯氨喹是一种有效的抗疟药物，适用于根治由间日疟原虫和卵形疟原虫引起的疟疾（1,2）。疟疾是一种通过蚊子传播的、由疟原虫感染引起的血液传播感染。间日疟原虫和卵形疟原虫对治疗构成了特殊挑战，因为其寄生生命周期包括一个休眠的、肝脏特异性阶段，该阶段对其他抗疟药物不敏感。因此，伯氨喹通常与其他疗法联合使用，如氯喹或基于青蒿素的药物，这些药物针对寄生虫的繁殖活跃形式。伯氨喹还用于预防由间日疟原虫（卵形疟原虫）引起的疟疾传播。单剂量低剂量（SLD）的伯氨喹具有杀配子体活性，虽不能治愈个体，但可控制疟疾传播。伯氨喹是一种前体药物，必须由细胞色素P450（CYP）酶系统激活。细胞色素P450成员2D6（CYP2D6）和细胞色素P450烟酰胺腺嘌呤二核苷酸磷酸（NADPH）：氧化还原酶（CPR）的代谢产生2种羟基化活性代谢产物，进而产生过氧化氢（HO）。这会对疟原虫和宿主人类细胞造成显著的氧化应激。葡萄糖-6-磷酸脱氢酶（G6PD）缺乏的个体尤其易受氧化应激影响，可能会发生急性溶血性贫血（AHA）。在开始使用伯氨喹疗程之前，个体应进行G6PD缺乏检测，以确保安全用药（1,2）。根据美国食品药品监督管理局（FDA）批准的药品标签，严重G6PD缺乏的个体不应服用伯氨喹（表1）（1）。世界卫生组织（WHO）建议，G6PD缺乏的个体应采用改良的伯氨喹治疗疗程。G6PD缺乏个体的推荐疗程是每周单剂量给药一次，共8周，而标准疗程是每日给药14天（表2）（2）。临床药物基因组学实施联盟（CPIC）报告称，G6PD缺乏个体接受伯氨喹治疗的不良反应风险与剂量相关，单剂量低剂量方案风险最低（表3）（3）。伯氨喹在孕期禁用，当婴儿的G6PD状态未知时，不建议哺乳期个体使用（1,2）。伯氨喹未被批准用于6个月以下的个体。患有易导致粒细胞减少的急性疾病的个体或正在服用其他溶血性药物的个体也禁用伯氨喹。（1）
