title: Pharmacokinetics of atazanavir/ritonavir among HIV-infected Thai children concomitantly taking tenofovir disoproxil fumarate.
abstract: BACKGROUND
  Atazanavir/ritonavir (ATV/r) is a recommended once-daily protease inhibitor. Tenofovir disoproxil fumarate (TDF) can reduce ATV exposure. The authors studied ATV pharmacokinetic (PK) parameters among children who received atazanavir/ritonavir co-administered with TDF.
  
  
  METHODS
  HIV-infected children aged 6-18 years with a body weight of 25-50 kg were eligible. Branded ATV 200 mg/capsule was taken with generic ritonavir 100 mg/tablet once daily plus TDF and lamivudine. A 24-hour PK study was performed at week 4 at t = 0 (pre-dose), 2, 4, 6, 8, 10, 12 and 24 hours. PK parameters were calculated using non-compartmental methods with WinNonlin software. Targeted ATV AUC 0-24 was 15 mg h/L and C trough was 0.15 mg/L. Comparisons of geometric means of ATV PK parameters between different weight bands were made using regression models.
  
  
  RESULTS
  Eighteen HIV-infected children with a median (IQR) age of 13 (11-14) years were enrolled. Median (range) body weight and body surface area were 35 (25-42) kg and 1.21 (0.96-1.35) m2, respectively. Median (IQR) CD4 cell count was 735 (540-1233) cells/mm3. Median (range) of ATV was 164 (145-209) mg/m2. Geometric mean (SD) ATV AUC 0-24 was 35.05 (1.06) mg h/L, and ATV C trough was 0.31 (1.13) mg/L. No child had ATV AUC 0-24 or C trough below target levels. There were no significant differences in PK parameters among weight bands.
  
  
  CONCLUSIONS
  Atazanavir/ritonavir 200/100 mg dosing provided adequate ATV AUC 0-24 when used with TDF in HIV-infected Thai children weighing between 25 and 50 kg.
authors.affiliation: From the *HIV-NAT, the Thai Red Cross AIDS Research Centre; †Division of Infectious Disease, Department of Pediatrics, Ramathibodi Hospital, Mahidol University; ‡SEARCH, the Thai Red Cross AIDS Research Centre; §Department of Internal Medicine, and ¶Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Torsak
authors.initials: T
authors.lastname: Bunupuradah
authors.forename: Chonnamet
authors.initials: C
authors.lastname: Techasaensiri
authors.forename: Siriwan
authors.initials: S
authors.lastname: Keadpudsa
authors.forename: Narukjaporn
authors.initials: N
authors.lastname: Thammajaruk
authors.forename: Amornrat
authors.initials: A
authors.lastname: Srimuan
authors.forename: Thaintip
authors.initials: T
authors.lastname: Sahakijpicharn
authors.forename: Wasana
authors.initials: W
authors.lastname: Prasitsuebsai
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Thanyawee
authors.initials: T
authors.lastname: Puthanakit
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D044466:Asian People; D000069446:Atazanavir Sulfate; D002648:Child; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D063065:Organophosphonates / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D019259:Lamivudine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; D019438:Ritonavir