title: Modified renal function in pregnancy: impact on emtricitabine pharmacokinetics.
abstract: OBJECTIVE
  The aims were to describe emtricitabine (FTC) pharmacokinetics in a large population of pregnant women during the different trimesters of pregnancy, and to explain FTC pharmacokinetic variability during pregnancy.
  
  
  METHODS
  FTC plasma concentrations were measured in 103 non-pregnant and 83 pregnant women, including women in the different trimesters of pregnancy and on the day of delivery. A total of 457 plasma concentrations were available for analysis. A population pharmacokinetic model was developed with Monolix 4.1.3.
  
  
  RESULTS
  FTC pharmacokinetics was best described by a two compartment model. The effect of creatinine clearance on apparent elimination clearance (CL/F) was significant. CL/F in pregnant women was significantly higher compared with non-pregnant women (geometric mean 24.1 vs 20.5 l h(-1) , P < 0.001), reflecting a modified renal function. FTC daily exposures (AUC) during pregnancy were lower than AUC in non-pregnant women, regardless of the trimester of pregnancy. FTC AUC geometric means were 8.38 mg l(-1 ) h in the second trimester of pregnancy, 8.16 mg l(-1 ) h in the third trimester of pregnancy, 8.30 mg l(-1 ) h on the day of delivery and 9.77 mg l(-1 ) h in non-pregnant women. FTC concentrations 24 h after administration were lower in pregnant women compared with non-pregnant women (0.054 vs. 0.079 mg l(-1) , P < 0.001) but still above the inhibitory concentration 50%.
  
  
  CONCLUSIONS
  FTC CL/F was increased by 18% during pregnancy, reflecting a modified renal function with 50% increase in estimated glomerular filtration rate. However, the impact of this modified renal function on FTC pharmacokinetics was not sufficiently large to consider dose adjustments during pregnancy.
authors.affiliation: EA08, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Unité de Recherche Clinique Paris Centre, AP-HP, Paris, France; DHU Risques et Grossesse, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Valade
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Tréluyer
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.forename: Elise
authors.initials: E
authors.lastname: Arrivé
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Pannier
authors.forename: Sihem
authors.initials: S
authors.lastname: Benaboud
authors.forename: Floris
authors.initials: F
authors.lastname: Fauchet
authors.forename: Naïm
authors.initials: N
authors.lastname: Bouazza
authors.forename: Frantz
authors.initials: F
authors.lastname: Foissac
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.forename: Déborah
authors.initials: D
authors.lastname: Hirt
mesh_terms: D019540:Area Under Curve; D003404:Creatinine / Q000097:blood; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068679:Emtricitabine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008954:Models, Biological; D011247:Pregnancy / Q000378:metabolism*
chemical_list: D003841:Deoxycytidine; D003404:Creatinine; D000068679:Emtricitabine
keywords: emtricitabine; population pharmacokinetics; pregnancy