title: Rilpivirine Pharmacokinetics Without and With Darunavir/Ritonavir Once Daily in Adolescents and Young Adults.
abstract: Rilpivirine (RPV), a recently developed, once daily human immunodeficiency virus non-nucleoside reverse transcriptase inhibitor, is not currently approved for pediatric patients, but is sometimes prescribed for adolescents with multiple treatment failures, for regimen simplification or to minimize toxicity. Darunavir/ritonavir (DRV/r) administered once daily is also increasingly used in adolescents and may alter RPV pharmacokinetics (PK). We evaluated the PK interactions between RPV and DRV/r once daily in adolescents and young adults.
  
  
  
  Human immunodeficiency virus-infected subjects 12 to <24 years old receiving a stable background therapy including RPV 25 mg once daily without or combined with DRV/r 800/100 mg once daily were enrolled. Intensive 24-hour blood sampling was performed, and PK indices were determined using noncompartmental analysis. Protocol-defined target drug exposure ranges based on adult data were used to assess the adequacy of each regimen.
  
  
  
  Fifteen subjects receiving RPV without and 14 subjects with DRV/r were enrolled. When dosed without DRV/r, the RPV geometric mean (90% confidence interval) for RPV AUC0-24, Cmax and C24 h were 2.38 μg h/mL (1.92-2.94), 0.14 μg/mL (0.12-0.18) and 0.07 μg/mL (0.03-0.10), respectively, similar to adult values. RPV concentrations were significantly increased with concomitant DRV/r use: RPV AUC24, Cmax and C24 h were 6.74 μg h/mL (4.89-9.28), 0.39 μg/mL (0.27-0.57) and 0.23 μg/mL (0.17-0.32), respectively, well above the target ranges based on adult data. DRV/r PK was not affected by coadministration of RPV.
  
  
  
  RPV PK in this adolescent population was similar to adults when dosed without DRV/r. DRV/r coadministration increased RPV exposure 2- to 3-fold, indicating that drug-related side effects should be closely monitored.
authors.affiliation: From the *Columbia University Medical Center, New York, NY; †Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL; ‡Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY; §National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Maternal and Pediatric Infectious Disease Branch, Bethesda, MD; ¶HJF-DAIDS, a Division of The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Contractor to NIAID, NIH, DHHS, Bethesda, MD; ‖Frontier Science & Technology, Amherst, NY; **Harvard School of Public Health, Boston, MA; ††Abbvie, Chicago, IL; ‡‡The University of Alabama at Birmingham, Birmingham, AL; and §§Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Marc
authors.initials: M
authors.lastname: Foca
authors.forename: Ram
authors.initials: R
authors.lastname: Yogev
authors.forename: Andrew
authors.initials: A
authors.lastname: Wiznia
authors.forename: Rohan
authors.initials: R
authors.lastname: Hazra
authors.forename: Patrick
authors.initials: P
authors.lastname: Jean-Philippe
authors.forename: Bobbie
authors.initials: B
authors.lastname: Graham
authors.forename: Paula
authors.initials: P
authors.lastname: Britto
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.forename: Jennifer
authors.initials: J
authors.lastname: King
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Tim R
authors.initials: TR
authors.lastname: Cressey
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D000069454:Darunavir / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D000068696:Rilpivirine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000068696:Rilpivirine; D019438:Ritonavir; D000069454:Darunavir