PMID- 23175556
OWN - NLM
STAT- MEDLINE
DCOM- 20130821
LR  - 20230613
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 56
IP  - 5
DP  - 2013 Mar
TI  - Effect of high-dose or split-dose artesunate on parasite clearance in 
      artemisinin-resistant falciparum malaria.
PG  - e48-58
LID - 10.1093/cid/cis958 [doi]
AB  - BACKGROUND: The emergence of Plasmodium falciparum resistance to artemisinins on 
      the Cambodian and Myanmar-Thai borders poses severe threats to malaria control. 
      We investigated whether increasing or splitting the dose of the short-half-life 
      drug artesunate improves parasite clearance in falciparum malaria in the 2 
      regions. METHODS: In Pailin, western Cambodia (from 2008 to 2010), and Wang Pha, 
      northwestern Thailand (2009-2010), patients with uncomplicated falciparum malaria 
      were randomized to oral artesunate 6 mg/kg/d as a once-daily or twice-daily dose 
      for 7 days, or artesunate 8 mg/kg/d as a once-daily or twice-daily dose for 3 
      days, followed by mefloquine. Parasite clearance and recrudescence for up to 63 
      days of follow-up were assessed. RESULTS: A total of 159 patients were enrolled. 
      Overall median (interquartile range [IQR]) parasitemia half-life (half-life) was 
      6.03 (4.89-7.28) hours in Pailin versus 3.42 (2.20-4.85) hours in Wang Pha (P = 
      .0001). Splitting or increasing the artesunate dose did not shorten half-life in 
      either site. Pharmacokinetic profiles of artesunate and dihydroartemisinin were 
      similar between sites and did not correlate with half-life. Recrudescent 
      infections occurred in 4 of 79 patients in Pailin and 5 of 80 in Wang Pha and was 
      not different between treatment arms (P = .68). CONCLUSIONS: Increasing the 
      artesunate treatment dose up to 8 mg/kg/d or splitting the dose does not improve 
      parasite clearance in either artemisinin resistant or more sensitive infections 
      with P. falciparum. Clinical Trials Registration. ISRCTN15351875.
FAU - Das, Debashish
AU  - Das D
AD  - Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, 
      Mahidol University, Bangkok, Thailand.
FAU - Tripura, Rupam
AU  - Tripura R
FAU - Phyo, Aung Pyae
AU  - Phyo AP
FAU - Lwin, Khin Maung
AU  - Lwin KM
FAU - Tarning, Joel
AU  - Tarning J
FAU - Lee, Sue J
AU  - Lee SJ
FAU - Hanpithakpong, Warunee
AU  - Hanpithakpong W
FAU - Stepniewska, Kasia
AU  - Stepniewska K
FAU - Menard, Didier
AU  - Menard D
FAU - Ringwald, Pascal
AU  - Ringwald P
FAU - Silamut, Kamolrat
AU  - Silamut K
FAU - Imwong, Mallika
AU  - Imwong M
FAU - Chotivanich, Kesinee
AU  - Chotivanich K
FAU - Yi, Poravuth
AU  - Yi P
FAU - Day, Nicholas P J
AU  - Day NP
FAU - Lindegardh, Niklas
AU  - Lindegardh N
FAU - Socheat, Duong
AU  - Socheat D
FAU - Nguon, Chea
AU  - Nguon C
FAU - White, Nicholas J
AU  - White NJ
FAU - Nosten, Francois
AU  - Nosten F
FAU - Dondorp, Arjen M
AU  - Dondorp AM
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 089275/WT_/Wellcome Trust/United Kingdom
GR  - 093956/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20121121
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Antibodies, Protozoan)
RN  - 0 (Antimalarials)
RN  - 0 (Artemisinins)
RN  - 0 (Immunoglobulin G)
RN  - 60W3249T9M (Artesunate)
RN  - 9RMU91N5K2 (artemisinin)
SB  - IM
CIN - Clin Infect Dis. 2013 Mar;56(5):694-6. PMID: 23175557
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Antibodies, Protozoan/blood
MH  - Antimalarials/*administration & dosage/pharmacokinetics
MH  - Artemisinins/*administration & dosage/pharmacokinetics/*therapeutic use
MH  - Artesunate
MH  - Cambodia
MH  - Child
MH  - *Drug Resistance
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Immunoglobulin G/blood
MH  - Malaria, Falciparum/*drug therapy/immunology
MH  - Male
MH  - Parasite Load
MH  - Parasitemia/*drug therapy
MH  - Plasmodium falciparum/*drug effects/immunology
MH  - Thailand
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC3563392
EDAT- 2012/11/24 06:00
MHDA- 2013/08/22 06:00
PMCR- 2012/11/21
CRDT- 2012/11/24 06:00
PHST- 2012/11/24 06:00 [entrez]
PHST- 2012/11/24 06:00 [pubmed]
PHST- 2013/08/22 06:00 [medline]
PHST- 2012/11/21 00:00 [pmc-release]
AID - cis958 [pii]
AID - 10.1093/cid/cis958 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2013 Mar;56(5):e48-58. doi: 10.1093/cid/cis958. Epub 2012 Nov 
      21.