PMID- 27191767
OWN - NLM
STAT- MEDLINE
DCOM- 20170110
LR - 20221207
IS - 0946-1965 (Print)
IS - 0946-1965 (Linking)
VI - 54
IP - 9
DP - 2016 Sep
TI - Pharmacokinetics of a nanocrystal-containing megestrol acetate formulation: a
single-dose, randomized, open-label, 2-part, 2-period crossover study in healthy
Korean subjects.
PG - 698-704
LID - 10.5414/CP202574 [doi]
AB - OBJECTIVE: The conventional suspension of megestrol acetate contains
micronized megestrol acetate, which was recently discovered to have a
disadvantage of decreasing bioavailability when taken in a fasting state. Since
megestrol acetate is taken to increase appetite, this property becomes a
discouraging factor. To improve upon this, an advanced formulation was developed
using a nanocrystal drug-delivery system. This study was conducted to compare the
safety and pharmacokinetic characteristics between the conventional formulation
of megestrol acetate and a generic version of the advanced formulation containing
nanocrystals. METHODS: This was a randomized, open-label, 2-period,
2-treatment, crossover, single-dose, 2-part study (part 1 fasting and part 2
fed), conducted in healthy males aged between 20 and 50 years with weight within
+/- 20% of ideal body weight having no congenital abnormalities or chronic
diseases. Different subjects were used in part 1 and part 2, but subjects
received a single dose of the reference and test drugs separated by a 14-day
washout period. Blood sampling was performed up to 120 hours after dosing using a
pre-specified sampling time scheme. Primary pharmacokinetic parameters were
Cmax and AUClast of the test and reference formulations of
megestrol acetate. Bioequivalence evaluation was based on the standard criterion
of 80 - 125% for the 90% confidence interval of geometric mean ratios of test to
reference drugs calculated for the pharmacokinetic parameters. To monitor adverse
events, both subject interviews and physical examinations were done on a regular
time basis. RESULTS: 80 subjects (n = 40 each part) were enrolled, and
79 completed the study. The 90% CIs of the geometric mean ratios of
Cmax and AUClast were 4.4625 - 5.6018 and 1.3602 - 1.6418,
respectively, for part 1, and 0.9793 - 1.1327 and 0.7721 - 0.8431, respectively,
for part 2. No significant difference was discovered in the incidence of adverse
events (AEs) when test and reference treated groups were compared.
CONCLUSIONS: Our findings suggest that the test formulation of
megestrol-acetate-containing nanocrystals is better absorbed and has higher
bioavailability compared to the reference formulation in a fasting state. This
should allow for a lower dose and better patient compliance.
ClinicalTrials.gov identifier: NCT02446353.
FAU - Chae, Dong Woo
AU - Chae DW
FAU - Son, Hankil
AU - Son H
FAU - Guk, Jinju
AU - Guk J
FAU - Park, Changhun
AU - Park C
FAU - Park, Kyungsoo
AU - Park K
LA - eng
SI - ClinicalTrials.gov/NCT02446353
PT - Comparative Study
PT - Journal Article
PT - Randomized Controlled Trial
PL - Germany
TA - Int J Clin Pharmacol Ther
JT - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN - 0 (Appetite Stimulants)
RN - 0 (Drugs, Generic)
RN - TJ2M0FR8ES (Megestrol Acetate)
SB - IM
MH - Adult
MH - Appetite Stimulants/administration & dosage/*pharmacokinetics
MH - Area Under Curve
MH - Asian People
MH - Biological Availability
MH - Cross-Over Studies
MH - Drug Delivery Systems
MH - Drugs, Generic/administration & dosage/adverse effects/*pharmacokinetics
MH - Fasting
MH - Humans
MH - Male
MH - Megestrol Acetate/administration & dosage/adverse effects/*pharmacokinetics
MH - Middle Aged
MH - *Nanoparticles
MH - Therapeutic Equivalency
MH - Young Adult
EDAT- 2016/05/19 06:00
MHDA- 2017/01/11 06:00
CRDT- 2016/05/19 06:00
PHST- 2016/08/17 00:00 [accepted]
PHST- 2016/05/19 06:00 [entrez]
PHST- 2016/05/19 06:00 [pubmed]
PHST- 2017/01/11 06:00 [medline]
AID - 14421 [pii]
AID - 10.5414/CP202574 [doi]
PST - ppublish
SO - Int J Clin Pharmacol Ther. 2016 Sep;54(9):698-704. doi: 10.5414/CP202574.