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Guidelines for the treatment of malaria – 2 edition

Antimalarials and protein-energy malnutrition
• Chloroquine
Few data are available for chloroquine kinetics in malnourished patients. Children with
kwashiorkor excreted a higher ratio of chloroquine to its metabolites before nutritional
rehabilitation (85). Presumably the metabolism of chloroquine by the liver was affected
adversely in protein-energy malnutrition. In a study of chloroquine pharmacokinetics
in five children with kwashiorkor (but without malaria), peak plasma concentrations
of the drug were approximately one-third of the values for healthy controls (mean 40 +
30 ng/ml compared with 134 + 99 ng/ml), but the times to peak levels and the elimination
half-lives were not significantly different, indicating reduced absorption. There was
also reduced metabolism of chloroquine to its metabolite, desethylchloroquine, which
suggested some impairment of drug metabolism. However, the study did not consider
plasma protein binding or drug distribution. Currently there are no recommendations
for dose alterations in patients with protein-energy malnutrition (86).
• Quinine

Three studies examining the kinetics of quinine in malnourished patients have been
published. The first from Nigeria compared the pharmacokinetics of an oral dose of
quinine 10 mg/kg in six children with kwashiorkor and seven normal controls who were
attending a malaria follow-up clinic (87). The children were aged 1–3 years. Values for total
plasma proteins and albumin for children with kwashiorkor were 74% and 67% of those
for control children. Absorption of quinine was slower in the kwashiorkor group than in
the controls (mean time to maximum concentration (t max) 2.5 ± 0.3 h compared with 1.5 ±
0.6 h); maximum plasma concentration (C max) was also lower (1.7 ± 0.5 μmol/l compared
with 2.4 + 0.3 μmol/l). Rate of clearance of quinine in kwashiorkor was less than one-third
of the value for well-nourished patients (31.5 ± 8.5 mg/min compared with 108.5 ± 34.8
mg/min) and the elimination half-life was also longer (15.0 ± 4.4 h compared with 8.0 ±
1.3 h). The authors concluded that the combination of malabsorption, reduced plasma
protein binding and reduced metabolism in the liver was responsible for the differences
observed. No dose alterations were suggested.
The second study, in Gabon, compared eight children with non-kwashiorkor global
malnutrition (defined as having a ratio of left mid-arm circumference:head circumference
of <0.279) with seven children with normal nutritional status (88). The children were aged
9–60 months. Only two were subsequently confirmed to have malaria, although all had
been febrile at presentation. Mean serum albumin levels in the two groups were 28.7 and
31.0 respectively. Each child received a loading dose of 16 mg/kg quinine base (25 mg/kg
quinine resorcine hydrochloride; Quinimax) by deep intramuscular injection followed by
8 mg/kg at 12 h. The t max was significantly shorter in malnourished children (1.1 ± 0.4 h
compared with 2.2 ± 1.2 h). No difference was observed for C max, volume of distribution
or protein binding. Clearance was significantly faster for malnourished children (4.4 ±

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