PMID- 25653564
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150205
LR  - 20200930
IS  - 1179-1438 (Print)
IS  - 1179-1438 (Electronic)
IS  - 1179-1438 (Linking)
VI  - 7
DP  - 2015
TI  - Bioavailability of everolimus administered as a single 5 mg tablet versus five 1 
      mg tablets: a randomized, open-label, two-way crossover study of healthy 
      volunteers.
PG  - 11-7
LID - 10.2147/CPAA.S73472 [doi]
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) inhibitor everolimus has a 
      well-established pharmacokinetics profile. We conducted a randomized, 
      single-center, open-label, two-sequence, two-period crossover study of healthy 
      volunteers to assess the relative bioavailability of everolimus administered as 
      one 5 mg tablet or five 1 mg tablets. METHODS: Subjects were randomized 1:1 to 
      receive everolimus dosed as one 5 mg tablet or as five 1 mg tablets on day 1, 
      followed by a washout period on days 8-14 and then the opposite formulation on 
      day 15. Blood sampling for pharmacokinetic evaluation was performed at 
      prespecified time points, with 17 samples taken for each treatment period. 
      Primary variables for evaluation of relative bioavailability were area under the 
      concentration-time curve from time zero to infinity (AUCinf) and maximum blood 
      concentration (Cmax). Safety was assessed by reporting the incidence of adverse 
      events (AEs). RESULTS: Twenty-two participants received everolimus as one 5 mg 
      tablet followed by five 1 mg tablets (n=11) or the opposite sequence (n=11). The 
      Cmax of five 1 mg tablets was 48% higher than that of one 5 mg tablet (geometric 
      mean ratio, 1.48; 90% confidence interval [CI], 1.35-1.62). AUCinf was similar 
      (geometric mean ratio, 1.08; 90% CI, 1.02-1.16), as were the extent of absorption 
      and the distribution and elimination kinetics. AEs, all grade 1 or 2, were 
      observed in 54.5% of subjects. CONCLUSION: Although the extent of absorption was 
      similar, the Cmax of five 1 mg tablets was higher than that of one 5 mg tablet, 
      suggesting these formulations lead to different peak blood concentrations and are 
      not interchangeable at the dose tested.
FAU - Thudium, Karen
AU  - Thudium K
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Gallo, Jorge
AU  - Gallo J
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Bouillaud, Emmanuel
AU  - Bouillaud E
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Sachs, Carolin
AU  - Sachs C
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Eddy, Simantini
AU  - Eddy S
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
FAU - Cheung, Wing
AU  - Cheung W
AD  - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
LA  - eng
PT  - Journal Article
DEP - 20150122
PL  - New Zealand
TA  - Clin Pharmacol
JT  - Clinical pharmacology : advances and applications
JID - 101564865
PMC - PMC4310326
OTO - NOTNLM
OT  - absorption kinetics
OT  - healthy volunteers
EDAT- 2015/02/06 06:00
MHDA- 2015/02/06 06:01
PMCR- 2015/01/22
CRDT- 2015/02/06 06:00
PHST- 2015/02/06 06:00 [entrez]
PHST- 2015/02/06 06:00 [pubmed]
PHST- 2015/02/06 06:01 [medline]
PHST- 2015/01/22 00:00 [pmc-release]
AID - cpaa-7-011 [pii]
AID - 10.2147/CPAA.S73472 [doi]
PST - epublish
SO  - Clin Pharmacol. 2015 Jan 22;7:11-7. doi: 10.2147/CPAA.S73472. eCollection 2015.