title: Pharmacokinetics of nevirapine in HIV-infected children under 3 years on rifampicin-based antituberculosis treatment.
abstract: OBJECTIVE
  There is an urgent need to optimize cotreatment for children with tuberculosis and HIV infection. We described nevirapine pharmacokinetics in Zambian children aged less than 3 years, cotreated with nevirapine, lamivudine and stavudine in fixed-dose combination (using WHO weight bands) and rifampicin-based antituberculosis treatment.
  
  
  METHODS
  Twenty-two children received antituberculosis and antiretroviral therapy (ART) concurrently for 4 weeks before pharmacokinetic sampling. Plasma nevirapine concentrations were determined in samples taken immediately before, and 1, 2 and 6 h after an observed dose. Nevirapine pharmacokinetics were compared with those in 16 children aged less than 3 years without tuberculosis.
  
  
  RESULTS
  Twenty-two children were treated for HIV/TB coinfection, 10 of whom were girls. One boy was excluded from analysis for nonadherence. The median age was 1.6 years (range: 0.7-3.2). Median weight was 8.0 kg (range: 5.1-10.5). The baseline CD4% was 13.1 (range: 3.9-43.6). Median predose concentration of nevirapine was 2.93 mg/l (range: 1.06-11.4), and peak concentration was 6.33 mg/l (range: 2.61-14.5). The nevirapine AUC up to 12 h was estimated as 52.0 mg.h/l (range: 22.6-159.7) compared with 90.9 mg.h/l (range: 40.4-232.1) in children without tuberculosis (P < 0.001). Predose concentrations of nevirapine were less than 3.0 mg/l in 11 children on tuberculosis treatment versus none of the 16 children without tuberculosis treatment (P = 0.001). AUC was 41% (95% CI: 23-54%) lower in children with tuberculosis than without tuberculosis (P < 0.001) after adjusting for dose per square meter.
  
  
  CONCLUSIONS
  : We found substantial reductions in nevirapine concentrations in young children receiving rifampicin. Further studies are needed to define the pharmacokinetics, safety and efficacy of adjusted doses of nevirapine-based ART in young children with tuberculosis.
authors.affiliation: Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: J Mirjam
authors.initials: JM
authors.lastname: Oudijk
authors.forename: Helen
authors.initials: H
authors.lastname: McIlleron
authors.forename: Veronica
authors.initials: V
authors.lastname: Mulenga
authors.forename: Chifumbe
authors.initials: C
authors.lastname: Chintu
authors.forename: Concepta
authors.initials: C
authors.lastname: Merry
authors.forename: A Sarah
authors.initials: AS
authors.lastname: Walker
authors.forename: Adrian
authors.initials: A
authors.lastname: Cook
authors.forename: Diana M
authors.initials: DM
authors.lastname: Gibb
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D016022:Case-Control Studies; D002675:Child, Preschool; D060085:Coinfection; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012293:Rifampin / Q000627:therapeutic use; D018119:Stavudine / Q000008:administration & dosage; D016896:Treatment Outcome; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy; D015024:Zambia
chemical_list: D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D012293:Rifampin