title: A pharmacokinetic comparison of adult and paediatric formulations of raltegravir in healthy adults.
abstract: BACKGROUND
  Raltegravir is an HIV-1 integrase inhibitor approved for use in adults, children and infants ≥4 weeks of age. As alternatives to the original film-coated tablet, a chewable ethylcellulose (EC) tablet and oral granules for suspension (GFS) have been developed for use in children. The purpose of this study was to evaluate these formulations in adults prior to use in paediatric studies.
  
  
  METHODS
  This open-label, 4-period, randomized, crossover study investigated the safety, tolerability and pharmacokinetics of raltegravir paediatric formulations and the effect of a high-fat meal on EC tablet pharmacokinetics in healthy adults. In a balanced, crossover design (with a 4-day washout between treatments), 12 subjects received one 400 mg film-coated tablet (fasted), four 100 mg EC tablets (fasted), one 400 mg GFS dose (fasted) and four 100 mg EC tablets (after a high-fat meal).
  
  
  RESULTS
  AUC0-∞ and Cmax were 2.6-fold and 4.6-fold higher for GFS and 1.8-fold and 3.2-fold higher for EC versus film-coated tablets. The geometric mean C12h values for the GFS formulation (162 nM) and the EC tablet (134 nM) were similar to that of the film-coated tablet (149 nM). Administration with a high-fat meal increased C12h, decreased Cmax and delayed Tmax for the EC tablet, but did not affect AUC0-∞. There were no serious adverse events (AEs) and no discontinuations due to drug-related clinical or laboratory AEs.
  
  
  CONCLUSIONS
  Both paediatric formulations demonstrate moderately higher AUC0-∞ and Cmax, and similar C12h compared with the film-coated tablet. These data support the use of raltegravir GFS and EC formulations in paediatric studies.
authors.affiliation: Merck & Co., Inc., Whitehouse Station, NJ, USA. elizabeth.rhee@merck.com.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Rhee
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Rizk
authors.forename: Diana M
authors.initials: DM
authors.lastname: Brainard
authors.forename: Isaias N
authors.initials: IN
authors.lastname: Gendrano
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.forename: Larissa A
authors.initials: LA
authors.lastname: Wenning
authors.forename: John A
authors.initials: JA
authors.lastname: Wagner
authors.forename: Marian
authors.initials: M
authors.lastname: Iwamoto
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D016903:Drug Monitoring; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D011760:Pyrrolidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium