title: Pharmacokinetic properties of sulfadoxine-pyrimethamine in pregnant women.
abstract: To determine the pharmacokinetic disposition of sulfadoxine (SDOX) and pyrimethamine (PYR) when administered as intermittent presumptive treatment during pregnancy (IPTp) for malaria, 30 Papua New Guinean women in the second or third trimester of pregnancy and 30 age-matched nonpregnant women were given a single dose of 1,500 mg of SDOX plus 75 mg of pyrimethamine PYR. Blood was taken at baseline and 1, 2, 4, 6, 12, 18, 24, 30, 48, and 72 h and at 7, 10, 14, 28, and 42 days posttreatment in all women. Plasma samples were assayed for SDOX, N-acetylsulfadoxine (NASDOX), and PYR by high-performance liquid chromatography. Population pharmacokinetic modeling was performed using NONMEM v6.2.0. Separate user-defined mamillary models were fitted to SDOX/NASDOX and PYR. When the covariate pregnancy was applied to clearance, there was a significant improvement in the base model for both treatments. Pregnancy was associated with a significantly lower area under the concentration-time curve from 0 to infinity for SDOX (22,315 versus 33,284 mg x h/liter), NASDOX (801 versus 1,590 mg x h/liter), and PYR (72,115 versus 106,065 microg x h/liter; P < 0.001 in each case). Because lower plasma concentrations of SDOX and PYR could compromise both curative efficacy and posttreatment prophylaxis in pregnant patients, IPTp regimens incorporating higher mg/kg doses than those recommended for nonpregnant patients should be considered.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Harin A
authors.initials: HA
authors.lastname: Karunajeewa
authors.forename: Sam
authors.initials: S
authors.lastname: Salman
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.forename: Francisca
authors.initials: F
authors.lastname: Baiwog
authors.forename: Servina
authors.initials: S
authors.lastname: Gomorrai
authors.forename: Irwin
authors.initials: I
authors.lastname: Law
authors.forename: Madhu
authors.initials: M
authors.lastname: Page-Sharp
authors.forename: Stephen
authors.initials: S
authors.lastname: Rogerson
authors.forename: Peter
authors.initials: P
authors.lastname: Siba
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Ilett
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D006801:Humans; D011247:Pregnancy; D011739:Pyrimethamine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013413:Sulfadoxine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine