PMID- 24608069
OWN - NLM
STAT- MEDLINE
DCOM- 20150805
LR  - 20151119
IS  - 2040-2058 (Electronic)
IS  - 1359-6535 (Linking)
VI  - 19
IP  - 6
DP  - 2014
TI  - A pharmacokinetic comparison of adult and paediatric formulations of raltegravir 
      in healthy adults.
PG  - 619-24
LID - 10.3851/IMP2765 [doi]
AB  - 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-infinity 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-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 AUC0-infinity 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.
FAU - Rhee, Elizabeth G
AU  - Rhee EG
AD  - Merck & Co., Inc., Whitehouse Station, NJ, USA. elizabeth.rhee@merck.com.
FAU - Rizk, Matthew L
AU  - Rizk ML
FAU - Brainard, Diana M
AU  - Brainard DM
FAU - Gendrano, Isaias N 3rd
AU  - Gendrano IN 3rd
FAU - Jin, Bo
AU  - Jin B
FAU - Wenning, Larissa A
AU  - Wenning LA
FAU - Wagner, John A
AU  - Wagner JA
FAU - Iwamoto, Marian
AU  - Iwamoto M
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20140307
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Pyrrolidinones)
RN  - 43Y000U234 (Raltegravir Potassium)
SB  - IM
MH  - Adult
MH  - Anti-HIV Agents/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Chemistry, Pharmaceutical
MH  - Cross-Over Studies
MH  - Drug Monitoring
MH  - Female
MH  - *Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pyrrolidinones/*administration & dosage/adverse effects/*pharmacokinetics
MH  - Raltegravir Potassium
MH  - Time Factors
EDAT- 2014/03/13 06:00
MHDA- 2015/08/06 06:00
CRDT- 2014/03/11 06:00
PHST- 2014/02/16 00:00 [accepted]
PHST- 2014/03/11 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2015/08/06 06:00 [medline]
AID - 10.3851/IMP2765 [doi]
PST - ppublish
SO  - Antivir Ther. 2014;19(6):619-24. doi: 10.3851/IMP2765. Epub 2014 Mar 7.