A pharmacokinetic comparison of adult and paediatric formulations of raltegravir in healthy adults

作者：Rhee Elizabeth G^*; Rizk Matthew L; Brainard Diana M; Gendrano Isaias N III; Jin Bo; Wenning Larissa A; Wagner John A; Iwamoto Marian

来源：Antiviral Therapy, 2014, 19(6): 619-624.

DOI：10.3851/IMP2765

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: AUC(0-infinity) and C-max 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 C-12h 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 C-12h, decreased C-max and delayed T-max for the EC tablet, but did not affect AUC(0-infinity). 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 AUC(0-infinity) and C-max, and similar C-12h compared with the film-coated tablet. These data support the use of raltegravir GFS and EC formulations in paediatric studies.

• 出版日期2014