title: Population analysis of the pregnancy-related modifications in lopinavir pharmacokinetics and their possible consequences for dose adjustment.
abstract: OBJECTIVE
  To investigate the possible necessity of an increase in lopinavir dose during pregnancy in order to achieve the concentrations previously defined as predictive of virological efficacy.
  
  
  METHODS
  Lopinavir pharmacokinetics were investigated by a population approach performed on 145 HIV-infected women, including 74 pregnant women. The final model was used to determine the probability of achievement of the target trough concentrations by Monte Carlo simulations.
  
  
  RESULTS
  The typical population estimates (inter-individual variability %) of apparent clearance (CL/F) and volume of distribution were 4.38 L/h (24%) and 58.4 L (59%), respectively. Pregnancy associated with a gestational age >15 weeks and delivery were found to increase lopinavir CL/F by 39% and 58%, respectively. With the standard 400 mg twice-a-day regimen, the probability of reaching the 1 mg/L target trough concentration for protease inhibitor (PI)-naive patients was 99% and 96% for non-pregnant and pregnant women, respectively. An important decrease in the probability of achieving the 5.7 mg/L target trough concentration for salvage therapy was observed for non-pregnant women (55%), this decrease being even greater for pregnant women (21%). Raising the lopinavir dose to 600 mg twice daily increased these probabilities to 87% and 53% for non-pregnant and pregnant women, respectively.
  
  
  CONCLUSIONS
  Modification of the lopinavir dose is unlikely to be required for PI-naive pregnant women; however, in pregnant women who have previously received a PI, therapeutic drug monitoring and/or empirical increasing of the dose should be considered.
authors.affiliation: Université Paris Descartes, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Bouillon-Pichault
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Elie
authors.initials: E
authors.lastname: Azria
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Pannier
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Firtion
authors.forename: Anne
authors.initials: A
authors.lastname: Krivine
authors.forename: Alexandra
authors.initials: A
authors.lastname: Compagnucci
authors.forename: Olivier
authors.initials: O
authors.lastname: Taulera
authors.forename: Laurent
authors.initials: L
authors.lastname: Finkielsztejn
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chhun
authors.forename: Gérard
authors.initials: G
authors.lastname: Pons
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Treluyer
mesh_terms: D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir; D008657:Metabolic Clearance Rate; D009010:Monte Carlo Method; D010949:Plasma / Q000737:chemistry; D011247:Pregnancy; D011744:Pyrimidinones / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D061466:Lopinavir