METABOLISM OF QUININE IN CHILDREN WITH GLOBAL MALNUTRITION

Malnutrition and malaria are two important public health problems in A frica. Quinine is one of the major treatments of chloroquine-resistant malaria. Although some authors have shown that quinine clearance is d ecreased in kwashiorkor, this type of malnutrition is caused by protei n deficiency that differs from global protein-energy malnutrition. In rats, hepatic metabolism of many drugs is decreased in protein deficie ncy and increased in global food restriction. Several studies have fou nd that human hepatic metabolism of many drugs is decreased in kwashio rkor, but, as yet, no study has focused on human global energy-protein malnutrition. Thus, as quinine is a drug with a narrow therapeutic in dex, we compared the pharmacokinetics of quinine in two groups. One gr oup included children with global malnutrition and the other was a con trol group of children with normal nutrition, Volume of distribution a nd plasma concentrations of unbound quinine did not differ between chi ldren with global malnutrition and children with normal nutritional st atus. Clearance was significantly faster, half-life shorter, and conce ntrations, 12 h after the beginning of treatment, lower in malnourishe d children compared with control subjects. The ratio between area unde r 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 incre ased in children with global malnutrition, we suggest that the adminis tration interval should be reduced in these children to obtain the sam e plasma concentrations of quinine found in normally nurished children . A safe and effective dosing strategy is postulated.