title: Pharmacokinetics of nevirapine in HIV-infected infants weighing 3 kg to less than 6 kg taking paediatric fixed dose combination tablets.
abstract: OBJECTIVE
  To evaluate pharmacokinetics of nevirapine, lamivudine and stavudine in HIV-infected Zambian infants receiving fixed dose combination (FDC) antiretroviral tablets (Triomune Baby).
  
  
  METHODS
  Phase I/II study.
  
  
  METHODS
  Sixteen HIV-infected children at least 1 month, weighing 3 kg to less than 6 kg were enrolled. Blood was sampled at t = 0, 2, 6 and 12 h after observed intake of one FDC tablet (50 mg nevirapine, 6 mg stavudine, 30 mg lamivudine) 4 weeks after starting treatment. Safety and viral load response over 48 weeks were determined.
  
  
  RESULTS
  The median [interquartile range (IQR)] age, body weight and daily nevirapine dose in 15 included children (eight girls) were 4.8 (4.2, 8.4) months, 5.3 (4.3, 5.5) kg and 348 (326 385) mg/m, respectively. The median (IQR) nevirapine area under the concentration-time curve (AUC0-12 h), Cmax and C12 h were 70 (56, 104) h mg/l, 7.5 (6.2, 10) mg/l, and 4.3 (2.9, 6.9) mg/l, respectively. Values were on average higher than reported in adults, but approximately 20% lower than previously reported in children weighing at least 6 kg. Four of 15 (27%) children had a subtherapeutic nevirapine C12 h (defined as <3.0 mg/l) compared to only three of 63 (5%) children weighing at least 6 kg (P = 0.02), whereas children aged less than 5 months [three of six (50%)] may have the highest risk for subtherapeutic nevirapine C12 h (P = 0.24). No association was found between viral load values and nevirapine plasma pharmacokinetic parameters (P > 0.3). Stavudine-lamivudine pharmacokinetic parameters were broadly comparable to heavier children.
  
  
  CONCLUSIONS
  Exposure to nevirapine in African, HIV-infected infants with low body weight taking FDC tablets appears on average to be adequate, but due to large intersubject variability a relatively high proportion had subtherapeutic nevirapine C12 h levels, particularly those aged less than 5 months.
authors: Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Q.Fillekes@akf.umcn.nl
authors: Quirine
authors: Q
authors: Fillekes
authors: Veronica
authors: V
authors: Mulenga
authors: Desiré
authors: D
authors: Kabamba
authors: Chipepo
authors: C
authors: Kankasa
authors: Margaret J
authors: MJ
authors: Thomason
authors: Adrian
authors: A
authors: Cook
authors: Alex
authors: A
authors: Ferrier
authors: Chifumbe
authors: C
authors: Chintu
authors: A Sarah
authors: AS
authors: Walker
authors: Diana M
authors: DM
authors: Gibb
authors: David M
authors: DM
authors: Burger
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active; D001835:Body Weight / Q000187:drug effects; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006679:HIV Seropositivity / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019259:Lamivudine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018119:Stavudine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019562:Viral Load; D015024:Zambia / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine