title: Steady-state pharmacokinetics of nevirapine extended-release tablets in HIV-1-infected children and adolescents: an open-label, multiple-dose, cross-over study.
abstract: BACKGROUND
  To compare steady-state (ss) pharmacokinetic targets of nevirapine extended-release (NVP-XR) tablets once-daily (QD) with immediate-release (NVP-IR) tablet or oral suspension twice-daily in HIV-1-infected children and adolescents.
  
  
  METHODS
  Phase I, open-label, multidose, cross-over study with optional extension phase, in 85 patients 3 to <18 years of age, previously on an NVP-IR-based regimen for ≥18 weeks with baseline viral load <50 copies/mL. Patients were stratified by age, treated with NVP-IR twice-daily for 11 days, then NVP-XR QD for 10 days. Cpre,ss (steady-state, predose concentrations) was obtained from all, and 12-hour NVP-IR and 24-hour NVP-XR steady-state pharmacokinetic profiles were obtained in the pharmacokinetic substudy. Viral loads, CD4 counts and adverse events (AEs) were monitored.
  
  
  RESULTS
  Eighty patients completed the trial. Adjusted geometric mean (gMean) Cpre,ss for NVP-XR and NVP-IR exceeded the target of 3000 ng/mL, and the adjusted gMean NVP-XR:NVP-IR ratio (90% confidence interval) for QD normalized and un-normalized Cpre,ss were 91.2% (83.5-99.6%) and 91.8% (83.7-100.7%). gMean 24-hour area under the curve at steady-state NVP-XR:NVP-IR for un-normalized dose was 90.4% and un-normalized Cpre,ss NVP-XR:NVP-IR were 91.0%, 81.9% and 103.7% for the 3 age groups, 3 to <6, 6 to <12 and 12 to <18 years, respectively. gMean values indicated no exposure to subtherapeutic NVP concentrations and viral suppression was adequate and maintained in all QD groups. Most AEs were mild and similar between age groups. No serious or Division of AIDS Grade 4 AEs or AE related treatment discontinuations occurred.
  
  
  CONCLUSIONS
  NVP-XR exhibited adequate trough concentrations with equivalent area under the curve at steady-state relative to NVP-IR. NVP-XR was well-tolerated and is a valuable treatment option for HIV-infected children and adolescents.
authors.affiliation: From the *Department of Pediatrics, University of Padua, Italy; †Botswana-Baylor Children's Clinical Centre of Excellence, Gaborone, Botswana; ‡Department of Pediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Germany; §Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa; ¶Tati River Clinic, Francistown, Botswana; ‖Department of Pediatrics, Goethe University, Frankfurt, Germany; and **Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT.
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Gabriel
authors.initials: G
authors.lastname: Anabwani
authors.forename: Cornelia
authors.initials: C
authors.lastname: Feiterna-Sperling
authors.forename: James
authors.initials: J
authors.lastname: Nuttall
authors.forename: Kgosidialwa
authors.initials: K
authors.lastname: Mompati
authors.forename: Christoph
authors.initials: C
authors.lastname: Königs
authors.forename: Federico J
authors.initials: FJ
authors.lastname: Mensa
authors.forename: John P
authors.initials: JP
authors.lastname: Sabo
authors.forename: Chan-Loi
authors.initials: CL
authors.lastname: Yong
authors.forename: Thomas R
authors.initials: TR
authors.lastname: MacGregor
authors.forename: Thuy
authors.initials: T
authors.lastname: Nguyen
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Quinson
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D013607:Tablets / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D013607:Tablets; D019829:Nevirapine