Metabolism of quinine in children with global malnutrition
Metabolism of quinine in children with global malnutrition
复制标题
DOI：
10.1203/00006450-199610000-00008
复制
发表时间：
1996-10-01
影响因子：
3.6
通讯作者：
Lagardere, B
中科院分区：
文献类型：
--
作者：
Treluyer, JM;Roux, A;Lagardere, B
营养不良和疟疾是非洲两个重要的公共卫生问题。奎宁是治疗耐氯喹疟疾的主要药物之一。尽管一些作者表明奎宁清除率在恶性营养不良中降低，但这种类型的营养不良是由蛋白质缺乏引起的，与整体蛋白质能量营养不良不同。在大鼠中，许多药物的肝脏代谢在蛋白质缺乏时减少，在全面食物限制时增加。多项研究发现，在恶性营养不良中，人体肝脏对许多药物的代谢降低，但迄今为止，还没有研究关注人类整体能量-蛋白质营养不良。因此，由于奎宁是一种治疗指数较窄的药物，我们比较了两组奎宁的药代动力学。一组包括全面营养不良儿童，另一组是营养正常儿童的对照组。全面营养不良儿童和营养状况正常儿童之间未结合奎宁的分布体积和血浆浓度没有差异。与对照组相比，营养不良儿童的清除速度明显更快，半衰期更短，并且开始治疗 12 小时后的浓度更低。羟基奎宁（人体奎宁的代谢物）曲线下面积与奎宁曲线下面积之比在营养不良儿童中显着增加，并且与中臂/头围比（儿童营养不良的标志）相关。因此，由于全球营养不良儿童的奎宁代谢增加，我们建议这些儿童应缩短给药间隔，以获得与正常营养儿童相同的奎宁血浆浓度。假定了安全有效的剂量策略。
Malnutrition and malaria are two important public health problems in Africa. Quinine is one of the major treatments of chloroquine-resistant malaria. Although some authors have shown that quinine clearance is decreased in kwashiorkor, this type of malnutrition is caused by protein deficiency that differs from global protein-energy malnutrition. In rats, hepatic metabolism of many drugs is decreased in protein deficiency and increased in global food restriction. Several studies have found that human hepatic metabolism of many drugs is decreased in kwashiorkor, but, as yet, no study has focused on human global energy-protein malnutrition. Thus, as quinine is a drug with a narrow therapeutic index, we compared the pharmacokinetics of quinine in two groups. One group included children with global malnutrition and the other was a control group of children with normal nutrition, Volume of distribution and plasma concentrations of unbound quinine did not differ between children with global malnutrition and children with normal nutritional status. Clearance was significantly faster, half-life shorter, and concentrations, 12 h after the beginning of treatment, lower in malnourished children compared with control subjects. The ratio between area under the curve of hydroxyquinine (metabolite of quinine in man) and area under the curve of quinine was significantly increased in malnourished children and correlated with mid-arm/head circumference ratio (marker of malnutrition in children). Thus, as metabolism of quinine is increased in children with global malnutrition, we suggest that the administration interval should be reduced in these children to obtain the same plasma concentrations of quinine found in normally nurished children. A safe and effective dosing strategy is postulated.