PMID- 21282434
OWN - NLM
STAT- MEDLINE
DCOM- 20110715
LR  - 20211020
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 55
IP  - 4
DP  - 2011 Apr
TI  - Pharmacokinetic properties of conventional and double-dose 
      sulfadoxine-pyrimethamine given as intermittent preventive treatment in infancy.
PG  - 1693-700
LID - 10.1128/AAC.01075-10 [doi]
AB  - Intermittent preventive treatment in infancy (IPTi) entails routine 
      administration of antimalarial treatment doses at specified times in at-risk 
      infants. Sulfadoxine-pyrimethamine (SDX/PYR) is a combination that has been used 
      as first-line IPTi. Because of limited pharmacokinetic data and suggestions that 
      higher milligram/kilogram pediatric doses than recommended should be considered, 
      we assessed SDX/PYR disposition, randomized to conventional (25/1.25 mg/kg of 
      body weight) or double (50/2.5 mg/kg) dose, in 70 Papua New Guinean children aged 
      2 to 13 months. Blood samples were drawn at baseline, 28 days, and three time 
      points randomly selected for each infant at 4 to 8 h or 2, 5, 7, 14, or 21 days. 
      Plasma SDX, PYR, and N(4)-acetylsulfadoxine (NSX, the principal metabolite of 
      SDX) were assayed by high-performance liquid chromatography (HPLC). Using 
      population modeling incorporating hepatic maturation and cystatin C-based renal 
      function, two-compartment models provided best fits for PYR and SDX/NSX plasma 
      concentration profiles. The area under the plasma concentration-time curve from 0 
      h to infinity (AUC(0-infinity)) was greater with the double dose versus the conventional 
      dose of PYR (4,915 versus 2,844 mug/day/liter) and SDX (2,434 versus 1,460 
      mg/day/liter). There was a 32% reduction in SDX relative bioavailability with the 
      double dose but no evidence of dose-dependent metabolism. Terminal elimination 
      half-lives (15.6 days for PYR, 9.1 days for SDX) were longer than previously 
      reported. Both doses were well tolerated without changes in hemoglobin or 
      hepatorenal function. Five children in the conventional and three in the 
      double-dose group developed malaria during follow-up. These data support the 
      potential use of double-dose SDX/PYR in infancy, but further studies should 
      examine the influence of hepatorenal maturation in very young infants.
FAU - Salman, Sam
AU  - Salman S
AD  - School of Medicine and Pharmacology, University of Western Australia, Perth, 
      Western Australia, Australia.
FAU - Griffin, Susan
AU  - Griffin S
FAU - Kose, Kay
AU  - Kose K
FAU - Pitus, Nolene
AU  - Pitus N
FAU - Winmai, Josephine
AU  - Winmai J
FAU - Moore, Brioni
AU  - Moore B
FAU - Siba, Peter
AU  - Siba P
FAU - Ilett, Kenneth F
AU  - Ilett KF
FAU - Mueller, Ivo
AU  - Mueller I
FAU - Davis, Timothy M E
AU  - Davis TM
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20110131
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antimalarials)
RN  - 0 (Drug Combinations)
RN  - 37338-39-9 (fanasil, pyrimethamine drug combination)
RN  - 5018-54-2 (N(4)-acetylsulfadoxine)
RN  - 88463U4SM5 (Sulfadoxine)
RN  - Z3614QOX8W (Pyrimethamine)
SB  - IM
MH  - Antimalarials/blood/*therapeutic use
MH  - Drug Combinations
MH  - Female
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Malaria, Falciparum/drug therapy/*prevention & control
MH  - Male
MH  - Pyrimethamine/blood/*therapeutic use
MH  - Sulfadoxine/analogs & derivatives/blood/*therapeutic use
PMC - PMC3067178
EDAT- 2011/02/02 06:00
MHDA- 2011/07/16 06:00
PMCR- 2011/10/01
CRDT- 2011/02/02 06:00
PHST- 2011/02/02 06:00 [entrez]
PHST- 2011/02/02 06:00 [pubmed]
PHST- 2011/07/16 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - AAC.01075-10 [pii]
AID - 1075-10 [pii]
AID - 10.1128/AAC.01075-10 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2011 Apr;55(4):1693-700. doi: 10.1128/AAC.01075-10. 
      Epub 2011 Jan 31.