High-Dose Chloroquine for Uncomplicated Plasmodium falciparum Malaria Is Well Tolerated and Causes Similar QT Interval Prolongation as Standard-Dose Chloroquine in Children.
Antimicrob Agents Chemother
; 64(3)2020 02 21.
Article
em En
| MEDLINE
| ID: mdl-31907183
ABSTRACT
Higher chloroquine doses can effectively treat up to 93 to 96% of malaria infections caused by Plasmodium falciparum carrying the resistance-conferring chloroquine resistance transporter (pfcrt) 76T allele. The tolerability of 50 (double the standard dose) and 70 mg/kg total chloroquine doses were assessed in this study. Fifteen 4- to 8-year-old children with uncomplicated malaria were given 10 mg/kg of chloroquine twice daily for 2 days and 5 mg/kg twice daily on the third day. Fifteen additional children were given 5 mg/kg twice daily for 2 more days. Chloroquine concentrations, blood pressure, electrocardiograms (ECGs), parasite density, and adverse events were assessed until day 28. Both dosages were well tolerated, and symptoms resolved by day 3 in parallel with increasing chloroquine concentrations. The median corrected QT (QTc) interval was 12 to 26 ms higher at expected peak concentrations than at day 0 (P < 0.001). Pfcrt 76T was associated with delayed parasite clearance. Day 28 clinical and parasitological responses against P. falciparum with pfcrt 76T were 57% (4/7) and 67% (4/6) after treatment with 50 and 70 mg/kg, respectively. Dosages were well tolerated, and no severe cardiac adverse events occurred. The QTc interval increase was similar to that found in adults taking 25 mg/kg of chloroquine. (This study has been registered at ClinicalTrials.gov under identifier NCT01814423.).
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
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Plasmodium falciparum
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Resistência a Medicamentos
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Proteínas de Protozoários
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Cloroquina
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Malária Falciparum
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Antimaláricos
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
Limite:
Child
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Child, preschool
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Female
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Humans
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Male
País/Região como assunto:
Africa
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2020
Tipo de documento:
Article