Publication: Chloroquine is grossly under dosed in young children with malaria: implications for drug resistance.
Accepted Date
2013-12-13
Issued Date
2014-01-23
Copyright Date
2014
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eng
ISSN
1932-6203 (Electronic)
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Mahidol University
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PLOS one
Bibliographic Citation
Ursing J, Eksborg S, Rombo L, Bergqvist Y, Blessborn D, Rodrigues A, et al. Chloroquine is grossly under dosed in young children with malaria: implications for drug resistance. PLoS One. 2014 Jan 23;9(1):e86801.
Suggested Citation
Ursing, Johan, Eksborg, Staffan, Rombo, Lars, Bergqvist, Yngve, Blessborn, Daniel, Rodrigues, Amabelia, Kofoed, Poul-Erik Chloroquine is grossly under dosed in young children with malaria: implications for drug resistance.. Ursing J, Eksborg S, Rombo L, Bergqvist Y, Blessborn D, Rodrigues A, et al. Chloroquine is grossly under dosed in young children with malaria: implications for drug resistance. PLoS One. 2014 Jan 23;9(1):e86801.. doi:10.1371/journal.pone.0086801 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/753
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Title
Chloroquine is grossly under dosed in young children with malaria: implications for drug resistance.
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Abstract
BACKGROUND: Plasmodium falciparum malaria is treated with 25 mg/kg of chloroquine
(CQ) irrespective of age. Theoretically, CQ should be dosed according to body
surface area (BSA). The effect of dosing CQ according to BSA has not been
determined but doubling the dose per kg doubled the efficacy of CQ in children
aged <15 years infected with P. falciparum carrying CQ resistance causing genes
typical for Africa. The study aim was to determine the effect of age on CQ
concentrations.
METHODS AND FINDINGS: Day 7 whole blood CQ concentrations were determined in 150
and 302 children treated with 25 and 50 mg/kg, respectively, in previously
conducted clinical trials. CQ concentrations normalised for the dose taken in
mg/kg of CQ decreased with decreasing age (p<0.001). CQ concentrations normalised
for dose taken in mg/m(2) were unaffected by age. The median CQ concentration in
children aged <2 years taking 50 mg/kg and in children aged 10-14 years taking 25
mg/kg were 825 (95% confidence interval [CI] 662-988) and 758 (95% CI 640-876)
nmol/l, respectively (p = 0.67). The median CQ concentration in children aged
10-14 taking 50 mg/kg and children aged 0-2 taking 25 mg/kg were 1521 and 549
nmol/l. Adverse events were not age/concentration dependent.
CONCLUSIONS: CQ is under-dosed in children and should ideally be dosed according
to BSA. Children aged <2 years need approximately double the dose per kg to
attain CQ concentrations found in children aged 10-14 years. Clinical trials
assessing the efficacy of CQ in Africa are typically performed in children aged
<5 years. Thus the efficacy of CQ is typically assessed in children in whom CQ is
under dosed. Approximately 3 fold higher drug concentrations can probably be
safely given to the youngest children. As CQ resistance is concentration
dependent an alternative dosing of CQ may overcome resistance in Africa.