title: The pharmacokinetics, safety and efficacy of boosted saquinavir tablets in HIV type-1-infected pregnant women.
abstract: BACKGROUND
  Pregnancy affects the pharmacokinetics of most protease inhibitors. Saquinavir, when administered in a tablet formulation, has not been studied extensively in this setting.
  
  
  METHODS
  A pharmacokinetic, prospective, multicentre trial of HIV type-1-infected pregnant women treated with saquinavir (500 mg tablets) boosted with ritonavir at a dose of 1,000/100 mg twice daily plus a nucleoside backbone was conducted. Pharmacokinetic curves were recorded for 12 h in the second trimester (week 20 +/-2), the third trimester (week 33 +/-2) and post-partum (weeks 4-6). Blood was sampled pre-dosing and at 1, 2, 3, 4, 6, 8, 10 and 12 h post-dosing. Pharmacokinetic parameters were calculated using WinNonlin software version 4.1.
  
  
  RESULTS
  A total of 37 women were included in the analysis. Mean (+/-sd) values for saquinavir area under the curve (AUC(0-12h)) were 23.47 h*mg/l (11.92) at week 20 (n=16), 23.65 h*mg/l (9.07) at week 33 (n=31) and 25.00 h*mg/l (11.81) post-partum (n=9). There was no significant difference in the saquinavir AUC(0-12h) when comparing the data during pregnancy and post-partum. Subtherapeutic plasma concentrations of saquinavir (defined as <0.10 mg/l) were not observed throughout the study. No major safety concerns were noted.
  
  
  CONCLUSIONS
  Saquinavir exposure in the new tablet formulation generates adequate saquinavir concentrations throughout the course of pregnancy and is safe to use; therefore, no dose adjustment during pregnancy is needed.
authors.affiliation: The HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand. jasper.v@hivnat.org
authors.forename: Jasper
authors.initials: J
authors.lastname: van der Lugt
authors.forename: Angela
authors.initials: A
authors.lastname: Colbers
authors.forename: Jose
authors.initials: J
authors.lastname: Molto
authors.forename: David
authors.initials: D
authors.lastname: Hawkins
authors.forename: Marchina
authors.initials: M
authors.lastname: van der Ende
authors.forename: Martin
authors.initials: M
authors.lastname: Vogel
authors.forename: Christoph
authors.initials: C
authors.lastname: Wyen
authors.forename: Malte
authors.initials: M
authors.lastname: Schutz
authors.forename: Peter
authors.initials: P
authors.lastname: Koopmans
authors.forename: Kiat
authors.initials: K
authors.lastname: Ruxrungtham
authors.forename: Clemens
authors.initials: C
authors.lastname: Richter
authors.forename: David
authors.initials: D
authors.lastname: Burger
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D015497:HIV-1; D006801:Humans; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use; D019258:Saquinavir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D013785:Thailand; D016896:Treatment Outcome
chemical_list: D017320:HIV Protease Inhibitors; D013607:Tablets; D019258:Saquinavir; D019438:Ritonavir