Document Detail


Use of area under the curve to evaluate the effects of antimalarial drugs on malaria-associated anemia after treatment.
MedLine Citation:
PMID:  20683244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
To evaluate the effects of antimalarial drugs on Plasmodium falciparum malaria-associated anemia, we use the area under the curve (AUC) of anemia levels after treatment as an approach to combine their duration and magnitude. The method involves numeric estimation, by trapezoidal rule, of AUC from a plot of deficit in hematocrit levels from 30% (the lower threshold of normal) versus time in anemic children. Using the method, we evaluated, in randomized trials, the effects of artesunate-mefloquine versus mefloquine alone and artemether-lumefantrine versus amodiaquine-artesunate on the time course of recovery from malaria-associated anemia in 109 children. Anemia resolution times were similar (10.9 ± 6.2 [standard deviation] versus 13.3 ± 8.9 days, P = 0.2), but mean AUC was significantly lower in artesunate-mefloquine- compared with mefloquine-treated children (35.5 ± 7.1 [standard error of mean] versus 49.8 ± 11.3 %·h, P = 0.02) indicating larger exposure to anemia in mefloquine-treated children. In artemether-lumefantrine- and amodiaquine-artesunate-treated children, both anemia resolution times (8.6 ± 5.3 [standard deviation] versus 8.6 ± 4.8 days, P = 0.98) and mean AUC (57.1 ± 12.9 [standard error of mean] versus 46.3 ± 8.7 %·h, P = 0.74) were similar. Estimation of AUC appears more robust than estimation of anemia resolution time in evaluating antimalarial drug effects and can be used in both observational studies and clinical trials assessing the effects of therapies on malaria-associated anemia.
Authors:
Akintunde Sowunmi; Grace Olusola Gbotosho; Christian Tientcha Happi; Onikepe Folarin; Titilope Okuboyejo; Obaro Michael; Bayo Fatunmbi
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of therapeutics     Volume:  18     ISSN:  1536-3686     ISO Abbreviation:  Am J Ther     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-13     Completed Date:  2012-01-09     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  9441347     Medline TA:  Am J Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  190-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amodiaquine / pharmacokinetics,  therapeutic use
Anemia / complications,  drug therapy*
Antimalarials / pharmacokinetics,  therapeutic use*
Area Under Curve*
Artemisinins / pharmacokinetics,  therapeutic use
Child
Child, Preschool
Drug Combinations
Ethanolamines
Female
Fluorenes / pharmacokinetics,  therapeutic use
Hematocrit
Humans
Infant
Malaria / complications,  drug therapy*
Malaria, Falciparum / drug therapy
Male
Mefloquine / pharmacokinetics,  therapeutic use
Nigeria
Plasmodium falciparum / drug effects
Grant Support
ID/Acronym/Agency:
R03 TW007757/TW/FIC NIH HHS; R03 TW007757-02/TW/FIC NIH HHS; R03TW007757-02/TW/FIC NIH HHS
Chemical
Reg. No./Substance:
0/Antimalarials; 0/Artemisinins; 0/Drug Combinations; 0/Ethanolamines; 0/Fluorenes; 0/amodiaquine, artesunate drug combination; 0/artemether-lumefantrine combination; 220236ED28/Amodiaquine; 83507-69-1/artesunate; TML814419R/Mefloquine
Comments/Corrections

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