title: Rifapentine Pharmacokinetics and Tolerability in Children and Adults Treated Once Weekly With Rifapentine and Isoniazid for Latent Tuberculosis Infection.
abstract: BACKGROUND
  In a phase 3, randomized clinical trial (PREVENT TB) of 8053 people with latent tuberculosis infection, 12 once-weekly doses of rifapentine and isoniazid had good efficacy and tolerability. Children received higher rifapentine milligram per kilogram doses than adults. In the present pharmacokinetic study (a component of the PREVENT TB trial), rifapentine exposure was compared between children and adults.
  
  
  METHODS
  Rifapentine doses in children ranged from 300 to 900 mg, and adults received 900 mg. Children who could not swallow tablets received crushed tablets. Sparse pharmacokinetic sampling was performed with 1 rifapentine concentration at 24 hours after drug administration (C24). Rifapentine area under concentration-time curve (AUC) was estimated from a nonlinear, mixed effects regression model (NLME).
  
  
  RESULTS
  There were 80 children (age: median, 4.5 years; range, 2-11 years) and 77 adults (age: median, 40 years; all ≥18 years) in the study. The geometric mean rifapentine milligram per kilogram dose was greater in children than in adults (children, 23 mg/kg; adults, 11 mg/kg). Rifapentine geometric mean AUC and C24 were 1.3-fold greater in children (all children combined) than in adults. Children who swallowed whole tablets had 1.3-fold higher geometric mean AUC than children who received crushed tablets, and children who swallowed whole tablets had a 1.6-fold higher geometric mean AUC than adults. The higher rifapentine doses in children were well tolerated. To obtain rifapentine exposures comparable in children to adults, dosing algorithms modeled by NLME were developed.
  
  
  CONCLUSIONS
  A 2-fold greater rifapentine dose for all children resulted in a 1.3-fold higher AUC compared to adults administered a standard dose. Use of higher weight-adjusted rifapentine doses for young children are warranted to achieve systemic exposures that are associated with successful treatment of latent tuberculosis infection in adults.
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio Veterans Administration Medical Center, San Antonio, Texas.
authors.forename: Marc
authors.initials: M
authors.lastname: Weiner
authors.affiliation: University of California at San Francisco, School of Pharmacy, Bioengineering and Therapeutic Sciences.
authors.forename: Radojka M
authors.initials: RM
authors.lastname: Savic
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: William R Mac
authors.initials: WR
authors.lastname: Kenzie
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio.
authors.forename: Diane
authors.initials: D
authors.lastname: Wing
authors.affiliation: University of Florida, College of Pharmacy, Gainesville.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Peloquin
authors.affiliation: Department of Medicine, University of Texas Health Science Center, San Antonio.
authors.forename: Melissa
authors.initials: M
authors.lastname: Engle
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Erin
authors.initials: E
authors.lastname: Bliven
authors.affiliation: Department of Pathology, University of Texas Health Science Center, San Antonio.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Prihoda
authors.affiliation: Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio.
authors.forename: Jonathan A L
authors.initials: JA
authors.lastname: Gelfond
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Scott
authors.affiliation: Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abdel-Rahman
authors.affiliation: Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kearns
authors.affiliation: Denver Health, Denver Public Health, Colorado.
authors.forename: William J
authors.initials: WJ
authors.lastname: Burman
authors.affiliation: Vanderbilt Universities, Medicine, Nashville, Tennessee.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sterling
authors.affiliation: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: M Elsa
authors.initials: ME
authors.lastname: Villarino
keywords: children; pharmacokinetics; rifapentine; treatment; tuberculosis.