title: Pharmacokinetics and pharmacodynamics of efavirenz and nelfinavir in HIV-infected children participating in an area-under-the-curve controlled trial.
abstract: Fifty human immunodeficiency virus (HIV)-infected children participated in an area-under-the plasma concentration-time curve (AUC)-controlled trial of efavirenz and nelfinavir. Pharmacokinetic evaluations were performed at weeks 2, 6, and 56. Efavirenz and nelfinavir doses were adjusted to achieve AUC values of 60-120 and > or = 10 mg h/l, respectively. Thirty-seven (74%) children met the efavirenz target and 41 (82%) the nelfinavir by week 10. Children with AUC values for both drugs above the first quartile were more likely to reach < 400 copies/ml of HIV RNA at week 8. Efavirenz and nelfinavir oral clearance increased 37 and 62% from weeks 2 to 56, respectively, in 34 children who continued on therapy at week 56. AUC values at week 56 were not different between children who did or did not have HIV RNA < 400 copies/ml. Dose adjustment to achieve specific AUC values in these children reduced the risk of suboptimal exposure and achieved high rates of virologic suppression.
authors.affiliation: Division of Infectious Diseases, Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Denver, Colorado, USA. courtney.fletcher@uchsc.edu
authors.forename: C V
authors.initials: CV
authors.lastname: Fletcher
authors.forename: R C
authors.initials: RC
authors.lastname: Brundage
authors.forename: T
authors.initials: T
authors.lastname: Fenton
authors.forename: C G
authors.initials: CG
authors.lastname: Alvero
authors.forename: C
authors.initials: C
authors.lastname: Powell
authors.forename: L M
authors.initials: LM
authors.lastname: Mofenson
authors.forename: S A
authors.initials: SA
authors.lastname: Spector
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000480:Alkynes; D019540:Area Under Curve; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003521:Cyclopropanes; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D019888:Nelfinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014481:United States; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019888:Nelfinavir; C098320:efavirenz