背景:在许多流行地区,间日疟原虫疟疾主要是年轻人和儿童的疾病。国际根治建议建议在所有年龄段的葡萄糖-6-磷酸脱氢酶正常患者中,建议固定目标剂量为0.25或0.5mg/kg/天的伯氨喹,持续14天。然而,对于许多抗疟疾药物来说,包括伯氨喹,有证据表明,在相同的体重调整剂量下,儿童的暴露量低于成人.该研究的目的是开发针对高频复发性热带间日疟原虫的14天基于体重和基于年龄的伯氨喹方案。
方法:推荐的成人目标剂量为0.5mg/kg/天(60kg患者为30mg)对热带间日疟原虫非常有效,并被认为可以产生最佳的药物暴露。使用异速缩放计算伯氨喹剂量,以在5至100kg的体重范围内得出基于体重的伯氨喹方案。生长曲线是从大湄公河次区域(GMS)的53,467个人的人体测量数据库中构建的,以定义体重与年龄的关系。与每个体重相关的中位年龄用于从基于体重的方案得出基于年龄的给药方案。
结果:建议的基于体重的方案具有5个给药范围:(i)5-7千克,5毫克,导致0.71-1.0毫克/千克/天;(ii)8-16千克,7.5mg,0.47-0.94毫克/千克/天;(iii)17-40千克,15毫克,0.38-0.88毫克/千克/天;(iv)41-80千克,30毫克,0.37-0.73毫克/千克/天;(v)81-100千克,45毫克,0.45-0.56mg/kg/天。相应的基于年龄的方案有4个给药带:6-11个月,5毫克,0.43-1.0毫克/千克/天;(ii)1-5年,7.5mg,0.35-1.25mg/kg/天;(iii)6-14年,15毫克,0.30-1.36mg/kg/天;(iv)≥15年,30毫克,0.35-1.07mg/kg/天。
结论:与基于年龄的方案相比,拟议的基于体重的方案在每个给药范围内显示出伯氨喹剂量的变异性较小,因此是首选方案。增加的剂量准确性可以通过两种方案的额外给药带来实现。基于年龄的方案可能不适用于GMS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告知建议的方案。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.