title: Pharmacokinetics of darunavir/ritonavir in Asian HIV-1-infected children aged ≥7 years.
abstract: BACKGROUND
  The Asian population, in general, has higher antiretroviral concentrations than those who are not Asian, but there are limited pharmacokinetic data for darunavir/ritonavir in Asian children.
  
  
  METHODS
  Thai children aged ≥7 years and with body weight (BW)≥20 kg who were on darunavir/ritonavir for ≥2 weeks underwent 12-h pharmacokinetics with blood sampling before and at 1, 2, 4, 6, 8, 10 and 12 h post-dosing. Darunavir/ritonavir doses were 375/100 mg twice daily (BW 20 to <30 kg, n=12), 450/100 mg twice daily (BW 30 to <40 kg, n=2) or 600/100 mg twice daily (BW ≥40 kg, n=5). Ritonavir 100 mg soft gel capsules were used instead of solution.
  
  
  RESULTS
  Of the 19 children, 8 were female, median age was 13 years (range 7-16) and median BW was 29.4 kg. The median duration of darunavir/ritonavir treatment was 11 months. The geometric mean values for darunavir were 60.3 h×mg/l for the area under the concentration-time curve at 0-12 h (AUC(0-12)), 8.3 mg/l for the maximum concentration (C(max)) and 3.1 for the concentration prior to the next dose (C(12)) with no differences between dosing groups. All had C(12) above the protein binding adjusted 50% effective concentration (EC(50)) of protease inhibitor-resistant virus (0.55 mg/l). The darunavir pharmacokinetic parameters were similar to those in non-Asian individuals from the DELPHI study, in which 13 of 20 with BW<40 kg used 50 or 60 mg ritonavir boosting.
  
  
  CONCLUSIONS
  Thai children aged ≥7 years who were on standard darunavir dosing with 100 mg ritonavir boosting had adequate and comparable darunavir AUC(0-12), C(max) and C(12) to non-Asian children who mainly used lower doses of ritonavir boosting. A ritonavir boosting dose of 100 mg can be used for children weighing ≥20 kg, particularly when lower dose formulations are unavailable or if intolerant to the solution.
authors.affiliation: Faculty of Medicine, Siriraj Hosptial, Mahidol University, Bangkok, Thailand.
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.forename: Wasana
authors.initials: W
authors.lastname: Prasitsuebsai
authors.forename: Orasri
authors.initials: O
authors.lastname: Wittawatmongkol
authors.forename: Meena
authors.initials: M
authors.lastname: Gorowara
authors.forename: Wanatpreeya
authors.initials: W
authors.lastname: Phongsamart
authors.forename: Jiratchiya
authors.initials: J
authors.lastname: Sophonphan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.forename: Nirun
authors.initials: N
authors.lastname: Vanprapar
authors.forename: Thanyawee
authors.initials: T
authors.lastname: Puthanakit
authors.forename: Chayapa
authors.initials: C
authors.lastname: Pasomsap
authors.forename: Tulathip
authors.initials: T
authors.lastname: Suwanlerk
authors.forename: Vanitha
authors.initials: V
authors.lastname: Sekar
authors.forename: David
authors.initials: D
authors.lastname: Burger
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D044466:Asian People; D001835:Body Weight; D002648:Child; D015331:Cohort Studies; D000069454:Darunavir; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013785:Thailand; D013997:Time Factors
chemical_list: D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D019438:Ritonavir; D000069454:Darunavir