PMID- 24378938
OWN - NLM
STAT- MEDLINE
DCOM- 20150128
LR  - 20140612
IS  - 1532-0987 (Electronic)
IS  - 0891-3668 (Linking)
VI  - 33
IP  - 7
DP  - 2014 Jul
TI  - Steady-state pharmacokinetics of nevirapine extended-release tablets in 
      HIV-1-infected children and adolescents: an open-label, multiple-dose, cross-over 
      study.
PG  - e173-9
LID - 10.1097/INF.0000000000000241 [doi]
AB  - 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.
FAU - Giaquinto, Carlo
AU  - Giaquinto C
AD  - From the *Department of Pediatrics, University of Padua, Italy; daggerBotswana-Baylor 
      Children's Clinical Centre of Excellence, Gaborone, Botswana; double daggerDepartment of 
      Pediatric Pneumology and Immunology, Charite-Universitatsmedizin Berlin, Germany; 
       section signDepartment of Paediatrics and Child Health, University of Cape Town, Cape Town, 
      South Africa;  paragraph signTati River Clinic, Francistown, Botswana;  ||Department of 
      Pediatrics, Goethe University, Frankfurt, Germany; and **Boehringer Ingelheim 
      Pharmaceuticals, Inc, Ridgefield, CT.
FAU - Anabwani, Gabriel
AU  - Anabwani G
FAU - Feiterna-Sperling, Cornelia
AU  - Feiterna-Sperling C
FAU - Nuttall, James
AU  - Nuttall J
FAU - Mompati, Kgosidialwa
AU  - Mompati K
FAU - Konigs, Christoph
AU  - Konigs C
FAU - Mensa, Federico J
AU  - Mensa FJ
FAU - Sabo, John P
AU  - Sabo JP
FAU - Yong, Chan-Loi
AU  - Yong CL
FAU - MacGregor, Thomas R
AU  - MacGregor TR
FAU - Nguyen, Thuy
AU  - Nguyen T
FAU - Quinson, Anne-Marie
AU  - Quinson AM
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pediatr Infect Dis J
JT  - The Pediatric infectious disease journal
JID - 8701858
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Tablets)
RN  - 99DK7FVK1H (Nevirapine)
SB  - IM
MH  - Adolescent
MH  - Anti-HIV Agents/administration & dosage/adverse 
      effects/*pharmacokinetics/pharmacology
MH  - CD4 Lymphocyte Count
MH  - Child
MH  - Child, Preschool
MH  - Cross-Over Studies
MH  - Delayed-Action Preparations/administration & dosage/adverse 
      effects/*pharmacokinetics/pharmacology
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - HIV Infections/drug therapy
MH  - Humans
MH  - Male
MH  - Nevirapine/administration & dosage/adverse effects/*pharmacokinetics/pharmacology
MH  - Tablets/administration & dosage/adverse effects/pharmacokinetics/pharmacology
MH  - Viral Load
EDAT- 2014/01/01 06:00
MHDA- 2015/01/30 06:00
CRDT- 2014/01/01 06:00
PHST- 2014/01/01 06:00 [entrez]
PHST- 2014/01/01 06:00 [pubmed]
PHST- 2015/01/30 06:00 [medline]
AID - 10.1097/INF.0000000000000241 [doi]
PST - ppublish
SO  - Pediatr Infect Dis J. 2014 Jul;33(7):e173-9. doi: 10.1097/INF.0000000000000241.