In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. The proposed weight-based regimen has 5 dosing bands: (i) 5–7 kg, 5 mg, resulting in 0.71–1.0 mg/kg/day; (ii) 8–16 kg, 7.5 mg, 0.47–0.94 mg/kg/day; (iii) 17–40 kg, 15 mg, 0.38–0.88 mg/kg/day; (iv) 41–80 kg, 30 mg, 0.37–0.73 mg/kg/day; and (v) 81–100 kg, 45 mg, 0.45–0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6–11 months, 5 mg, 0.43–1.0 mg/kg/day; (ii) 1–5 years, 7.5 mg, 0.35–1.25 mg/kg/day; (iii) 6–14 years, 15 mg, 0.30–1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35–1.07 mg/kg/day. The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.

中文翻译：

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开发基于体重和年龄的伯氨喹每日剂量，用于根治间日疟疾


在许多流行地区，间日疟原虫疟疾主要是青壮年和儿童的疾病。国际根治建议建议对所有年龄段的葡萄糖-6-磷酸脱氢酶正常患者使用伯氨喹的固定目标剂量为 0.25 或 0.5 mg/kg/天，持续 14 天。然而，对于包括伯氨喹在内的许多抗疟疾药物，有证据表明，在相同体重调整剂量下，儿童的暴露量低于成人。该研究的目的是开发针对高频率复发的热带间日疟原虫的 14 天基于体重和基于年龄的伯氨喹治疗方案。推荐的成人目标剂量为 0.5 mg/kg/天（60 kg 患者为 30 mg），对热带间日疟原虫非常有效，并被认为可产生最佳药物暴露。使用异速生长缩放法计算伯氨喹剂量，得出基于体重的伯氨喹治疗方案，体重范围为 5 至 100 kg。生长曲线是根据来自大湄公河次区域 (GMS) 的 53,467 名个体的人体测量数据库构建的，以确定体重与年龄的关系。与每个体重相关的中位年龄用于从基于体重的方案推导出基于年龄的给药方案。拟议的基于体重的方案有 5 个剂量范围：(i) 5-7 kg，5 mg，即 0.71-1.0 mg/kg/天； (ii) 8-16公斤，7.5毫克，0.47-0.94毫克/公斤/天； (iii) 17-40公斤，15毫克，0.38-0.88毫克/公斤/天； (iv) 41-80公斤，30毫克，0.37-0.73毫克/公斤/天； (v) 81–100 公斤、45 毫克、0.45–0.56 毫克/公斤/天。相应的基于年龄的方案有4个剂量范围：6-11个月，5毫克，0.43-1.0毫克/公斤/天； (ii) 1-5年，7.5毫克，0.35-1.25毫克/公斤/天； (iii) 6-14岁，15毫克，0.30-1.36毫克/公斤/天； (iv) ≥ 15 岁，30 毫克，0.35–1.07 毫克/公斤/天。 与基于年龄的方案相比，所提出的基于体重的方案显示每个剂量范围内伯氨喹剂量的变异性较小，因此是优选的。通过两种方案的额外剂量范围可以提高剂量准确性。基于年龄的治疗方案可能不适用于大湄公河次区域以外的地区，必须基于当地的人体测量数据。迫切需要幼儿的药代动力学数据来为建议的治疗方案提供信息。