title: Pharmacokinetics of saquinavir-SGC in HIV-infected pregnant women.
abstract: OBJECTIVE
  To evaluate saquinavir (SQV) pharmacokinetics, tolerance, and safety in 10 HIV-infected pregnant women between 14-32 weeks gestation.
  
  
  METHODS
  This was a phase I, prospective, area-under-the-curve (AUC) targeted study. Antepartum treatment consisted of SQV 1200 mg tid, lamivudine 150 mg bid, and zidovudine 200 mg tid. The SQV targeted exposure was an 8-hour AUC (AUC(8)) of 3000 ng. h/mL; the study was to be halted if the first 4 participants did not achieve this AUC(8). Cord blood and plasma samples were collected in neonates at birth.
  
  
  RESULTS
  Four women completed the SQV pharmacokinetic assessments. Exposure in all 4 patients was below the target AUC(8). Median (range) AUC(8) and trough (C8H) were 1672 (738-2614) ng. h/mL and 60 (<15-332) ng/mL, respectively. Oral clearance (CL/F) was 9.3 (5.1-16.6) L/h/kg and C(max) was 599 (177-953) ng/mL. Cord and neonate plasma concentrations were mostly undetectable; 1 of 5 infants was HIV-infected at 24 weeks.
  
  
  CONCLUSIONS
  These data suggest highly variable SQV pharmacokinetics in pregnant women, and exposure at 1200 mg tid may not be adequate for longer term therapy; both the AUC(8) and C8H were considerably below average. Because ritonavir has been shown to significantly increase SQV concentrations, this combination should be further explored in this population.
authors.affiliation: Division of Clinical Pharmacology, University of Alabama at Birmingham, 35294-0019, USA. EAcosta@uab.edu
authors.forename: E P
authors.initials: EP
authors.lastname: Acosta
authors.forename: C
authors.initials: C
authors.lastname: Zorrilla
authors.forename: R
authors.initials: R
authors.lastname: Van Dyke
authors.forename: A
authors.initials: A
authors.lastname: Bardeguez
authors.forename: E
authors.initials: E
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Hughes
authors.forename: S
authors.initials: S
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Pitt
authors.forename: H
authors.initials: H
authors.lastname: Watts
authors.forename: L
authors.initials: L
authors.lastname: Mofenson
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D019540:Area Under Curve; D002214:Capsules; D004359:Drug Therapy, Combination; D005260:Female; D005780:Gelatin; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000635:transmission; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D019259:Lamivudine / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019258:Saquinavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D002214:Capsules; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D005780:Gelatin; D019258:Saquinavir