title: Pharmacokinetics of Once-Daily Darunavir/Ritonavir With and Without Etravirine in Human Immunodeficiency Virus-Infected Children, Adolescents, and Young Adults.
abstract: BACKGROUND
  Limited data are available for once-daily (QD) darunavir (DRV)/ritonavir (r) in the pediatric population. Coadministration of etravirine (ETR) may alter the pharmacokinetics (PK) of DRV. We evaluated the PK interactions between DRV/r (QD) and ETR QD or twice-daily (BID) in children, adolescents, and young adults.
  
  
  METHODS
  Human immunodeficiency virus-infected subjects 9 to < 24 years old on optimized background therapy including DRV/r 800/100 mg QD alone or combined with ETR 200 mg BID or ETR 400 mg QD were enrolled. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen. Intensive 24-hour blood sampling was performed, and PK parameters were determined using noncompartmental analysis.
  
  
  RESULTS
  Thirty-one subjects (14 males) completed the study; 16 received DRV/r QD alone (group 1), 6 received DRV/r plus ETR BID (group 2A), and 9 received DRV/r plus ETR QD (group 2B). The geometric mean (90% confidence interval [CI] geometric mean) for DRV area under the curve at 24 hours (AUC24) was 57.9 (49.6-67.6), 74.9 (44.4-126.5), and 66.4 (50.8-86.9) mg × h/L for patients in groups 1, 2A, and 2B, respectively. The increased DRV exposure when coadministered with ETR was not statistically significant. The geometric mean (90% CI geometric mean) of ETR AUC24 was 8.6 (4.4-16.8) and 11.9 (7.5-18.9) mg × h/L for groups 2A and 2B, respectively, with comparable C24.
  
  
  CONCLUSIONS
  The results suggest that DRV/r QD with ETR 400 mg QD or 200 mg BID is appropriate and support further evaluation of the safety and efficacy of the once-daily regimen in older children, adolescents, and young adults.
authors.affiliation: University of Alabama at Birmingham.
authors.forename: Kajal B
authors.initials: KB
authors.lastname: Larson
authors.affiliation: Program for HIV Prevention and Treatment, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
authors.affiliation: Children's Memorial Hospital, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.affiliation: Jacobi Medical Center, Bronx, New York.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wiznia
authors.affiliation: National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maternal and Pediatric Infectious Disease Branch, Bethesda, Maryland.
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.affiliation: HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.
authors.forename: Patrick
authors.initials: P
authors.lastname: Jean-Philippe
authors.affiliation: Frontier Science & Technology, Amherst, New York.
authors.forename: Bobbie
authors.initials: B
authors.lastname: Graham
authors.affiliation: Frontier Science & Technology, Amherst, New York.
authors.forename: Amy
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Paula
authors.initials: P
authors.lastname: Britto
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.affiliation: University of Alabama at Birmingham.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D000069454:Darunavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage*; D011743:Pyrimidines; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013449:Sulfonamides; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D013449:Sulfonamides; C451734:etravirine; D019438:Ritonavir; D000069454:Darunavir
keywords: antiretrovirals; darunavir; etravirine; pediatrics; pharmacokinetics; ritonavir