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Amaç: Fenofibrat ve statinlerle kombinasyon tedavisi,
karışık dislipideminin tedavisinde güncel klinik kılavuzlar
tarafından şiddetle tavsiye edilmektedir. Bu çalışmada,
fenofibratın farmakokinetik profilini değiştirerek, bu
kombinasyon tedavisinin eş zamanlı uygulanmasına bağlı kas
toksisitesi riskini azaltmak ve modifiye salımlı
formülasyonun oral biyoyararlanımını iyileştirmek için
inovatif bir geciktirilmiş salımlı fenofibrat preparatı
formüle edilmiştir.Yöntemler: Fenofibrat, çok-partiküllü
pelet kaplama öncesinde toz katmanlama işlemi yoluyla ilaç
yüklü çekirdekleri hazırlamak için mikronize edilmiştir.
Farklı kaplama formülasyonları taranmış ve bunların in vitro
salım profilleri, ticari yavaş salımlı peletler Lipilfen®
ile karşılaştırılmıştır.. Optimize edilmiş iki formülasyon,
Beagle köpeklerinde değerlendirilmiş ve fenofibratın iki
referans ticari preparatı (çabuk salımlı preparasyon
Lipanthyl® ve yavaş salımlı peletler Lipilfen®) ile
karşılaştırılmıştır. Sonuçlar: In vitro testlerden seçilen
R1 ve R2'den fenofibratın in vivo salımı için bir gecikme
fazı, ardından hızlı ve tam ilaç salımı gözlenmiştir. R1 ve
R2'nin bağıl biyoyararlanımı sırasıyla %100.4 ve %201.1
olarak kaydedilmiştir ve bu oranlar Lipilfen® ile tespit
edilenden (%67.2) daha yüksek olmuştur.
Yorum: Modifiye fenofibrat, gelişmiş biyoyararlanım ve
geciktirilmiş salım özellikleri göstermiştir ve statinlerle
birlikte uygulandığında güvenliliği ve tedaviye uyumu
potansiyel olarak iyileştirebilir. Bildiğimiz kadarıyla bu,
fenofibratın geciktirilmiş salımlı preparatına ilişkin ilk
bildiridir.
Purpose:
Combination therapy of Ffenofibrate and statins
combination therapy is highly recommended by the current clinical guidelines
for the 1treatment of
combinedmixed2 dyslipidemia. In this study,
we formulated 3an innovative delayed-release preparation of
fenofibrate
was designed to
achieve the following: to
reduce the risk of muscle toxicity, caused by
simultaneous administration of this combination therapy,
by altering the pharmacokinetic profile of fenofibrate, as
well as to improve the oral bioavailability of the
modified-release formulation.
Methods:
Micronized fFenofibrate was
usedmicronized to
prepare drug-loaded cores via a powder layering process
before multiparticulate pellet coating. Different coating
formulations were screened, and their in vitro release
profiles was
compared with the commercial sustained-release pellets
Lipilfen®. Two optimized formulations were evaluated in
Beagle dogs
using and compared with 4two commercial preparations of fenofibrate (the
immediate release preparation Lipanthyl® and the sustained
release pellets Lipilfen®) as references.
Results: The in vivo release of fenofibrate from R1 and
R2 selected from in vitro tests exhibited a lag phase,
and thenfollowed by 5rapid and complete drug release. The relative
bioavailabilities of R1 and R2 were 100.4% and 201.1%,
respectively, which were greater than that of Lipilfen®
(67.2%).
Conclusion: The modified fenofibrate pellets
developed showed enhanced
bioavailability and delayed-release properties. They have
the potential to improve safety and compliance when co-administratedadministered
6with statins. This is the first report of a
delayed-release fenofibrate preparation.
Purpose:
Combination1According to current guidelines.combination therapy of Ffenofibrate and statins
combination therapy is highly recommended
by the current clinical guidelines
for
the 2treatment oftreating combinedmixed3 dyslipidemia. In this study,
we formulated 4an innovative delayed-release preparation of
fenofibrate
was designed to
achieve the following: to
reduce the risk of muscle toxicity,
caused by simultaneous administration of this
combination therapy,
by altering the pharmacokinetic profile of fenofibrate,
as well asand to improve
the oral bioavailability of the modified-release
formulation.
Methods:
Micronized fFenofibrate was
usedmicronized
and used to
prepare drug-loaded cores via a powder-5layering process before
performing 6multiparticulate pellet coating.
Different coating formulations were screened, and their in
vitro release
profiles waswere compared
with those of the
commercial sustained-release pellets Lipilfen®. Two
optimized formulations were evaluated in Beagle dogs
using7 models and compared with two
reference commercial preparations of fenofibrate (, Lipanthyl®(the immediate-release preparation Lipanthyl®) and
Lipilfen®(the sustained-release pellets
Lipilfen®) as references).
Results: The in vivo release of fenofibrate from R1 and
R2 (selected from in vitro tests)
exhibited a lag phase,
and thenwhich was followed by 8rapid and complete drug release. The relative
bioavailabilities of R1 and R2 were 100.4% and 201.1%,
respectively, which
were greater9were higher
than that of Lipilfen® (67.2%).
Conclusion:
The modifiedModified
fenofibrate pellets
developed showed enhanced
bioavailability and delayed-release
properties. They have the potential toproperties and can
improve safety and compliance when co-administratedadministered10 with statins.
This To the best of our knowledge, this
is the first report of a delayed-release
preparation of fenofibrate preparation11.
Purpose: According to current guidelines.combination therapy
of fenofibrate and statins is highly recommended for
treating mixed dyslipidemia. In this study, we formulated an
innovative delayed-release preparation of fenofibrate to
reduce the risk of muscle toxicity, by altering the
pharmacokinetic profile of fenofibrate and to improve the
oral bioavailability of the modified-release formulation.
Methods: Fenofibrate was micronized and used to prepare
drug-loaded cores via a powder-layering process before
performing multiparticulate pellet coating. Different
coating formulations were screened, and their in vitro
release profiles were compared with those of the commercial
sustained-release pellets Lipilfen®. Two optimized
formulations were evaluated in Beagle dogs models and
compared with two reference commercial preparations of
fenofibrate, Lipanthyl®(the immediate-release preparation)
and Lipilfen®(the sustained- release pellets) .
Results: The in vivo release of fenofibrate from R1 and R2
(selected from in vitro tests) exhibited a lag phase, which
was followed by rapid and complete drug release. The
relative bioavailabilities of R1 and R2 were 100.4% and
201.1%, respectively, which werehigher than that of
Lipilfen® (67.2%).
Conclusion: Modified fenofibrate pellets showed enhanced
bioavailability and delayed-release propertiesand can
improve safety and compliance when co-administered with
statins. To the best of our knowledge, this is the first
report of a delayed-release preparation of fenofibrate.
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Resmi, şirket içi iletişim belgeleri ve şirket dışı kullanılan belgeler
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Nature Publishing Group | Nature; 459, 712-716 (4 June 2009) | 36.10 | Frequent inactivation of A20 in B-cell lymphomas | Kato Motohiro |
Blackwell Publishing Ltd | Cellular Microbiology ; doi: 10.1111/ j.1462-5822.2011.01733.x | 6.00 | Salmonella type III effector SpvC, a phosphothreonine lyase, contributes to reduction in inflammatory response during intestinal phase of infection | Haneda Takeshi |
The Company of Biologists | Journal of Cell Science; March 1, 2010 123, 756-766. | 6.00 | Retromer-mediated direct sorting is required for proper endosomal recycling of the mammalian iron transporter, DMT1 | Tabuchi Mitsuaki |
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