title: Pharmacokinetics of pediatric lopinavir/ritonavir tablets in children when administered twice daily according to FDA weight bands.
abstract: BACKGROUND
  Lopinavir/ritonavir (LPV/r) pediatric tablets (100/25 mg) are approved by the United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) as part of combination antiretroviral therapy. Dosing is based on body weight bands or body surface area under FDA approval and only body surface area by the EMA. This can lead to a different recommended dose. In addition, weight band-based dosing has not been formally studied in the target population. We evaluated the pharmacokinetics (PK) of LPV/r in children, administered twice daily according to the FDA weight bands, using pediatric tablets.
  
  
  METHODS
  Fifty-three HIV-infected children were included in the PK substudy of the Paediatric European Network for the Treatment of AIDS 18 trial (KONCERT). In this study, children were randomized to receive LPV/r twice or once daily, according to FDA weight bands. A PK assessment was performed in 17, 16 and 20 children in the 15-25 kg, ≥ 25-35 kg and >35 kg weight band, respectively, while children took the tablets twice daily. Rich sampling was performed, and PK parameters were calculated by noncompartmental analysis. Given the high percentage of Asian children, it was also tested whether there was a difference in PK parameters between Asian and non-Asian children.
  
  
  RESULTS
  For the total group, LPV geometric mean AUC0-12, Cmax and C12 were 106.9 h × mg/L, 12.0 mg/L and 4.9 mg/L, respectively. There were no significant differences in LPV PK parameters between the weight bands. In addition, weight was not found to be associated with variability in Cmax, C12 or AUC0-12 for the LPV PK parameters.
  
  
  CONCLUSIONS
  FDA weight band-based dosing recommendations provide adequate exposure to LPV when using LPV/r pediatric tablets.
authors.affiliation: From the *Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; †MRC, Clinical Trials Unit, London, United Kingdom; ‡Imperial College Healthcare NHS Trust, Department of Pediatrics, St Mary's Hospital, London, United Kingdom; §Program for HIV Prevention and Treatment/IRD UMI-174, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; ¶Department of Pediatrics, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; ‖Department of Pediatrics, Nakornping Hospital, Chiang Mai, Thailand; **Unitat d´Infectologia, Servei de Pediatria, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain; ††Department of Pediatrics and Adolescent Medicine, J.W. Goethe University, Frankfurt, Germany; ‡‡INSERM, SC10-US19, Villejuif, France; and §§Department of Pediatrics, University of Padova, Italy.
authors.forename: Diane E T
authors.initials: DE
authors.lastname: Bastiaans
authors.forename: Silvia
authors.initials: S
authors.lastname: Forcat
authors.forename: Hermione
authors.initials: H
authors.lastname: Lyall
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.forename: Rawiwan
authors.initials: R
authors.lastname: Hansudewechakul
authors.forename: Suparat
authors.initials: S
authors.lastname: Kanjanavanit
authors.forename: Antoni
authors.initials: A
authors.lastname: Noguera-Julian
authors.forename: Christoph
authors.initials: C
authors.lastname: Königs
authors.forename: Jamie R J
authors.initials: JR
authors.lastname: Inshaw
authors.forename: Suwalai
authors.initials: S
authors.lastname: Chalermpantmetagul
authors.forename: Yacine
authors.initials: Y
authors.lastname: Saïdi
authors.forename: Alexandra
authors.initials: A
authors.lastname: Compagnucci
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Harper
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Angela P H
authors.initials: AP
authors.lastname: Colbers
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D001835:Body Weight; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D061466:Lopinavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013607:Tablets
chemical_list: D017320:HIV Protease Inhibitors; D013607:Tablets; D061466:Lopinavir; D019438:Ritonavir