title: Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum.
abstract: OBJECTIVE
  Our objective was to evaluate the pharmacokinetics of nelfinavir (NFV) (625 mg tablets) 1250 mg twice daily during pregnancy and postpartum.
  
  
  METHODS
  The participants were HIV-1-infected pregnant women enrolled in P1026s and receiving NFV (625 mg tablets) 1250 mg twice daily as part of routine clinical care. Intensive steady-state 12-h NFV pharmacokinetic profiles were performed during pregnancy and postpartum. The target NFV area under the plasma concentration-time curve (AUC(0-12)) was >or=10th percentile NFV AUC(0-12) in non-pregnant historical controls (18.5 microg h/mL).
  
  
  RESULTS
  Of 27 patients receiving NFV, pharmacokinetic data were available for four (second trimester), 27 (third trimester) and 22 (postpartum) patients. The NFV maximum concentration (C(max)), 12-h post-dose concentration (C(12)) and AUC(0-12) were significantly lower during the third trimester compared to postpartum (P<or=0.03). The metabolite hydroxyl-tert-butylamide (M8) AUC(0-12) and the M8/NFV AUC ratio were lower during the third trimester compared to postpartum (P<0.01). The NFV AUC(0-12) exceeded the AUC(0-12) target for 15/27 (56%) and 21/22 (95%) of third trimester and postpartum patients, respectively. The minimum concentration (C(min)) was above the suggested minimum trough concentration (0.8 mug/mL) in 15% (third trimester) and 18% (postpartum). The plasma viral load was <400 HIV-1 RNA copies/mL in 81% of patients at delivery.
  
  
  CONCLUSIONS
  These results suggest that higher doses of NFV should be considered during pregnancy.
authors.affiliation: Pediatric, Adolescent and Maternal AIDS Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-7510, USA. jennifer_read@nih.gov
authors.forename: J S
authors.initials: JS
authors.lastname: Read
authors.forename: B M
authors.initials: BM
authors.lastname: Best
authors.forename: A M
authors.initials: AM
authors.lastname: Stek
authors.forename: C
authors.initials: C
authors.lastname: Hu
authors.forename: E V
authors.initials: EV
authors.lastname: Capparelli
authors.forename: D T
authors.initials: DT
authors.lastname: Holland
authors.forename: S K
authors.initials: SK
authors.lastname: Burchett
authors.forename: M E
authors.initials: ME
authors.lastname: Smith
authors.forename: E C
authors.initials: EC
authors.lastname: Sheeran
authors.forename: W T
authors.initials: WT
authors.lastname: Shearer
authors.forename: I
authors.initials: I
authors.lastname: Febo
authors.forename: M
authors.initials: M
authors.lastname: Mirochnick
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn; D019888:Nelfinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000378:metabolism; D011645:Puerperal Infection / Q000188:drug therapy / Q000378:metabolism; D012367:RNA, Viral; D019562:Viral Load; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019888:Nelfinavir
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