PMID- 20547795
OWN - NLM
STAT- MEDLINE
DCOM- 20101201
LR  - 20211020
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 54
IP  - 9
DP  - 2010 Sep
TI  - New fixed-dose artesunate-mefloquine formulation against multidrug-resistant 
      Plasmodium falciparum in adults: a comparative phase IIb safety and 
      pharmacokinetic study with standard-dose nonfixed artesunate plus mefloquine.
PG  - 3730-7
LID - 10.1128/AAC.01187-09 [doi]
AB  - A new fixed-dose artesunate (AS)-mefloquine (MQ) was assessed in adults 
      hospitalized for 28 days with uncomplicated drug-resistant falciparum malaria. 
      The patients (n = 25/arm) were treated with (i) two fixed-dose tablets (AS-MQ 
      arm; 100 mg AS-200 mg MQ/tablet) daily for 3 days (days 0, 1, and 2) or (ii) 
      nonfixed AS (AS-plus-MQ arm; 4 mg/kg of body weight/day for 3 days) plus MQ (15 
      mg/kg on day 1 and 10 mg/kg on day 2), dosed by weight. Clinical laboratory 
      electrocardiogram (ECG), adverse events (AEs), efficacy, and pharmacokinetic 
      parameters were assessed over 28 days. Both regimens were well tolerated. No AEs 
      were drug related. Two serious AEs of malaria-induced hypotension occurring in 
      the AS-MQ arm necessitated rescue treatment. There were no significant changes in 
      hematology, biochemistry, or PR and QRS intervals. For all patients, mean 
      Fridericia-corrected QT intervals were significantly (P < or = 0.0027) prolonged 
      on day 3 (407 ms) and day 7 (399 ms) versus day 0 (389 ms), in parallel with 
      significant (P < or = 0.0003) falls in heart rates (67 [day 3], 73 [day 7], and 
      83 [day 0] beats/minute). Fixed-nonfixed formulations were bioequivalent for MQ, 
      but not for AS and dihydroartemisinin (DHA). One AS-MQ patient developed a new 
      infection on day 28; his day 28 plasma MQ concentration was 503.8 ng/ml. 
      Fixed-dose AS-MQ was well tolerated, had pharmacokinetic (PK) profiles broadly 
      similar to those of nonfixed AS plus MQ, and is a suitable replacement.
FAU - Krudsood, S
AU  - Krudsood S
AD  - Hospital for Tropical Disease, Bangkok, Thailand.
FAU - Looareesuwan, S
AU  - Looareesuwan S
FAU - Tangpukdee, N
AU  - Tangpukdee N
FAU - Wilairatana, P
AU  - Wilairatana P
FAU - Phumratanaprapin, W
AU  - Phumratanaprapin W
FAU - Leowattana, W
AU  - Leowattana W
FAU - Chalermrut, K
AU  - Chalermrut K
FAU - Ramanathan, S
AU  - Ramanathan S
FAU - Navaratnam, V
AU  - Navaratnam V
FAU - Olliaro, P
AU  - Olliaro P
FAU - Vaillant, M
AU  - Vaillant M
FAU - Kiechel, J R
AU  - Kiechel JR
FAU - Taylor, W R J
AU  - Taylor WR
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20100614
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antimalarials)
RN  - 0 (Artemisinins)
RN  - 60W3249T9M (Artesunate)
RN  - TML814419R (Mefloquine)
SB  - IM
EIN - Antimicrob Agents Chemother. 2010 Oct;54(10):4526
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antimalarials/administration & dosage/adverse 
      effects/*pharmacokinetics/pharmacology/*therapeutic use
MH  - Artemisinins/administration & dosage/adverse 
      effects/*pharmacokinetics/pharmacology/*therapeutic use
MH  - Artesunate
MH  - Drug Resistance, Multiple
MH  - Female
MH  - Humans
MH  - Malaria, Falciparum/*drug therapy/metabolism/pathology
MH  - Male
MH  - Mefloquine/administration & dosage/adverse 
      effects/*pharmacokinetics/pharmacology/*therapeutic use
MH  - Middle Aged
MH  - Plasmodium falciparum/drug effects
MH  - Treatment Outcome
MH  - Young Adult
PMC - PMC2935027
EDAT- 2010/06/16 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/03/01
CRDT- 2010/06/16 06:00
PHST- 2010/06/16 06:00 [entrez]
PHST- 2010/06/16 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - AAC.01187-09 [pii]
AID - 1187-09 [pii]
AID - 10.1128/AAC.01187-09 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2010 Sep;54(9):3730-7. doi: 10.1128/AAC.01187-09. 
      Epub 2010 Jun 14.