title: Pharmacokinetics of nelfinavir and its active metabolite, hydroxy-tert-butylamide, in infants perinatally infected with human immunodeficiency virus type 1.
abstract: BACKGROUND
  In children younger than 2 years of age vertically infected with HIV-1, the recommended pediatric dosing regimen for nelfinavir (20 to 30 mg/kg three times a day) provides insufficient drug exposure. This study was conducted to determine the steady state pharmacokinetics of nelfinavir and its active metabolite, M8, in this population.
  
  
  METHODS
  Fourteen infants (2.3 to 8.5 months) underwent 18 intensive pharmacokinetic studies of nelfinavir and M8 at steady state. Nelfinavir and M8 concentrations were measured by high performance liquid chromatography coupled with mass spectrometry, and individual pharmacokinetic values were determined.
  
  
  RESULTS
  A mean nelfinavir daily dose of 135.7 +/- 18.8 mg/kg (twice or three times a day) resulted in median C(min), C(max), area under the plasma concentration-time curve (AUC(0-24 h)) and CL/ for nelfinavir of 0.627 mg/l, 2.39 mg/l, 30.6 mg*h/l and 4.2 liters/h/kg, respectively. When normalized for a daily dose of nelfinavir of 150 mg/kg/day, 16.7% of C(max) and 27.8% of AUC(0-24 h) values were below the tenth percentile for adult values.
  
  
  CONCLUSIONS
  During the first year of life, nelfinavir requirement is much higher than in older children and adults to obtain similar drug exposure. The mechanisms underlying such differences may involve higher first past metabolism and/or drug interactions or might be related to feeding conditions.
authors.affiliation: Department of Pediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Litalien
authors.forename: Albert
authors.initials: A
authors.lastname: Faye
authors.forename: Alexandra
authors.initials: A
authors.lastname: Compagnucci
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Lynda
authors.initials: L
authors.lastname: Harper
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: Evelyne
authors.initials: E
authors.lastname: Jacqz-Aigrain
mesh_terms: D016049:Didanosine / Q000378:metabolism / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D019888:Nelfinavir / Q000378:metabolism / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D018119:Stavudine / Q000378:metabolism / Q000494:pharmacology
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D019888:Nelfinavir; D016049:Didanosine