研究業績
S. Nishiyama, Y. Takemoto, K. Yamanouchi, K. Kondo, S. Kawatsu, M. Maruyama,
K. Higaki. Dynamic changes in the distribution equilibrium of drugs in
nanoemulsions associated with drug absorption facilitate the absorption
improvement for poorly water-soluble drugs by SNEDDS. Int. J. Pharm., 674,
125458 (2025)
M. Maruyama, R. Torii, H. Matsui, H. Hayashi, K. Ogawara, K. Higaki. Repeated
sequential administration of pegylated emulsion of SU5416 and liposomal
paclitaxel enhances anti-tumor effect in 4T1 breast cancer-bearing mice.
Eur. J. Pharm. Biopharm., 209, 114663 (2025)
M. Maruyama, T. Ueda, Y. Ienaka, H. Tojo, K. Hyodo, K. Ogawara, K. Higaki.
EGF-induced P-gp expression in tumor vasculature contributes to therapeutic
resistance to doxorubicin-PEG-liposomes in mice bearing doxorubicin-resistant
B16-BL6 tumors. J. Drug Deliv. Sci. Technol., 106, 106690 (2025)
S. Aikawa, H. Tanaka, H. Ueda, M. Maruyama, K. Higaki. Specific intermolecular
interaction with sodium glycocholate generates the co-amorphous system
showing higher physical stability and aqueous solubility of Y5 receptor
antagonist of neuropeptide Y, a brick dust molecule. Eur J Pharm Biopharm.,
202, 114395 (2024)
M. Maruyama, H. Matsui, H. Nakamura, R. Torii, Y. Takasugi, K. Ogawara,
K. Higaki. Vascular normalization with pegylated emulsion of SU5416 enhances
anti-tumor effect of liposomal paclitaxel in 4T1 breast cancer-bearing
mice: Analysis of intratumoral vessels and microenvironment. J. Drug Deliv.
Sci. Technol., 96, 105647 (2024)
T. Inoue, S. Maehara, M. Maruyama, K. Higaki. Combination of co-amorphization
with SNEDDS outperforms Ofev® in the oral absorption of nintedanib. Int
J Pharm., 657, 124197 (2024)
H. Mukai, M. Takanashi, K. Ogawara, M. Maruyama, K. Higaki. Possible Regulation
of P-Glycoprotein Function by Adrenergic Agonists II: Study with Isolated
Rat Jejunal Sheets and Caco-2 Cell monolayers. J Pharm Sci., 113 (5), 1209-1219
(2024).
T. Shehata, Y. Kono, K. Higaki, T. Kimura and K. Ogawara: In vivo distribution
characteristics and anti-tumor effect of doxorubicin encapsulated in PEG-modified
niosomes in solid tumor-bearing mice. J. Drug Deliv. Sci. and Technol.,
80, 104122 (2023).
Y. Takamura, S. Kikuzawa, M. Fujihara, Y. Sunatsuki, H. Ota, K. Higaki
and H. Kakuta: Characterization and interconversion of two crystal forms
of Net-3IB, a retinoid X receptor agonist. Chem. Pharm. Bull., 71 (4),
282-288 (2023).
M. Gomi, N. Mizutani, R. Senoo, N. Matsubara, A. Watanabe, M. Maruyama,
G. Kimura, K. Higaki. Development of Sustained Release System Based on
High Water-Absorbable Gel Formation Using Croscarmellose Sodium, Alkaline
Excipients and HPMC (ACSH SR System); Novel Application of Croscarmellose
Sodium as a Gel Former. Pharm Res., 40, 3073-3086 (2023)
M. Maruyama, M. Yoshikata, M. Sakaguchi, S. Wakushima, K. Higaki. Establishment
of a novel in vitro co-culture system of enteric neurons and Caco-2 cells
for evaluating the effect of enteric nervous system on transepithelial
transport of drugs. Int. J. Pharm., 633, 122617 (2023)
K. Yamanouchi, T. Ishimaru, T. Kakuno, Y. Takemoto, S. Kawatsu, K. Kondo,
M. Maruyama, K. Higaki. Improvement and characterization of oral absorption
behavior of clofazimine by SNEDDS: Quantitative evaluation of extensive
lymphatic transport. Eur. J. Pharm. Biopharm., 187, 141-155 (2023).
S. Aikawa, H. Tanaka, H. Ueda, M. Maruyama, K. Higaki. Formation of a Stable
Co-Amorphous System for a Brick Dust Molecule by Utilizing Sodium Taurocholate
with High Glass Transition Temperature. Pharmaceutics., 15, 84 (2023).
S. Nakashima, T. Iwamoto, M. Takanashi, K. Ogawara, M. Maruyama, K. Higaki:
Effect of Excessive Serotonin on Pharmacokinetics of Cephalexin after Oral
Administration: Studies with Serotonin-Excessive Model Rats: Pharm. Res.,
39, 2163-2178 (2022).
M. Onishi, K. Tagawa, M. Jiko, K. Koike, M. Maruyama, H. Hashizume, K.
Imagaki, K. Higaki: Efficient Evaluation of In Vivo Performance in Human
for Generic Formulation by Novel Dissolution-Absorption Prediction (DAP)
Workflow: Pharm. Res., 39, 2203-2216 (2022).
M. Maruyama, Y. Nishida, H. Tanaka, T. Minami, K.I. Ogawara, M. Miyake,
Y. Takamura, H. Kakuta, K. Higaki: Analysis of absorption-enhancing mechanisms
for combinatorial use of spermine with sodium taurocholate in Caco-2 cells.
Eur. J. Pharm. Biopharm., 180, 332-343 (2022).
Y. Kono, A. Fushimi, Y. Yoshizawa, K. Higaki and K. Ogawara: Effects of
particle size and release property of paclitaxel-loaded nanoparticles on
their peritoneal retention and therapeutic efficacy against mouse malignant
ascites: Int. J. Pharm., 623, 121904 (2022).
Y. Sumimoto, S. Okawa, T. Inoue, K. Masuda, M. Maruyama, K. Higaki. Extensive
improvement of oral bioavailability of mebendazole, a brick dust, by polymer-containing
SNEDDS preparation: Disruption of high crystallinity by utilizing its counter
ion. Eur. J. Pharm. Biopharm.,172, 213-227 (2022)
M. Maruyama, H. Tojo, K. Toi, Y. Ienaka, K. Hyodo, H. Kikuchi, K. Ogawara,
and K. Higaki: Effect of Doxorubicin Release Rate From Polyethylene Glycol-Modified
Liposome on Anti-tumor Activity in B16-BL6 Tumor-Bearing Mice. J. Pharm.
Sci., 111, 293-297, (2022).
T. Minamisakamoto, S. Nishiguchi, K. Hashimoto, K. Ogawara, M. Maruyama,
and K. Higaki: Sequential administration of PEG-Span 80 niosome enhances
anti-tumor effect of doxorubicin-containing PEG liposome. Eur. J. Pharm.
Biopharm., 169, 20-28 (2021).
H. Mukai, M. Takanashi, K. Ogawara, M. Maruyama, and K. Higaki: Possible
Regulation of P-glycoprotein Function by Adrenergic Agonists in a Vascular-luminal
Perfused Preparation of Small Intestine. J. Pharm. Sci., 110 (12), 3889-3895
(2021).
S. Okawa, Y. Sumimoto, K. Masuda, K. Ogawara, M. Maruyama and K. Higaki:
Improvement of lipid solubility and oral bioavailability of a poorly water-
and poorly lipid-soluble drug, rebamipide, by utilizing its counter ion
and SNEDDS preparation. Eur. J. Pharm. Sci., 159, 105721 (2021).
M. Miyake, T. Minami, M. Maruyama, T. Mukai and K. Higaki: Spermine with
sodium taurocholate enhances pulmonary absorption of macromolecules in
rats. J. Pharm. Sci., 110 (10), 3464-3470 (2021).
M. Maruyama, Y. Nakano, T. Nishimura, R. Iwata, S. Matsuda, M. Hayashi,
Y. Nakai, M. Nonaka and T. Sugimoto: PC3-secreted microprotein is expressed
in glioblastoma stem-like cells and human glioma tissues. Biol. Pharm.
Bull., 44 (7), 910-919 (2021).
K. Kohara, A. Inoue, Y. Nakano, H. Hirai, T. Kobayashi, M. Maruyama, R.
Baba and C. Kawashima: BATTLE: Genetically Engineered Strategies for Split-Tunable
Allocation of Multiple Transgenes in the Nervous System. iScience, 23 (6),
101248 (2020).
R. Iwata, J. Hyoung Lee, M. Hayashi, U. Dianzani, K. Ofune, M. Maruyama,
S. Oe, T. Ito, T. Hashiba, K. Yoshimura, M. Nonaka, Y. Nakano, Norian L.,
I. Nakano and A. Asai: ICOSLG-mediated regulatory T-cell expansion and
IL-10 production promote progression of glioblastoma. Neuro. Oncol., 22
(3), 333-344 (2020).
K. Okada, A. Sato, A. Hiramoto, R. Isogawa, Y. Kurosaki, K. Higaki, S-I.
Miyoshi, K-S. Chang and H-S. Kim: Pharmacokinetic analysis of new synthetic
antimalarial N-251. Trop. Med. Health, 47, 40 (2019).
D. Inoue, A. Tanaka, S. Kimura, A. Kiriyama, H. Katsumi, A. Yamamoto, K.
Ogawara, T. Kimura, K. Higaki, R. Yutani, T. Sakane, T. Furubayashi: The
relationship between in vivo nasal drug clearance and in vitro nasal mucociliary
clearance: Application to the prediction of nasal drug absorption: Eur.
J. Pharm. Sci., 117, 21-26 (2018).
D. Inoue, S. Kimura, A. Kiriyama, H. Katsumi, A. Yamamoto, K. Ogawara,
K. Higaki, A. Tanaka, R. Yutani, T. Sakane, T. Furubayashi: Quantitative
estimation of the effect of nasal mucociliary function on in vivo absorption
of norfloxacin after intranasal administration to rats: Mol. Pharm., 15
(10), 4462-4469 (2018).
The involvement of cancer stem cells in brain metastatic process. R. Iwata,
M. Maruyama, K. Ofune, Y. Nakano, S. Oe, M. Hayashi, K. Yoshimura, M. Nonaka
and A Asai: Cytometry Res., 28 (1), 13-18 (2018).
R. Iwata, M. Maruyama, T. Ito, Y. Nakano, Y. Kanemura, T. Koike, S. Oe,
K. Yoshimura, M. Nonaka, S. Nomura, T. Sugimoto, H. Yamada and A. Asai:
Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine
tumor. Med. Mol. Morphol., 50 (4), 211-219 (2017).
S. Kozai, T. Wada, K. Ogawara, T. Kida, H. Tokushige and K. Higaki: Evaluation
of pharmacokinetic-pharmacodynamic indices of topical ophthalmic gatifloxacin
against Staphylococcus aureus utilizing an in-vitro aqueous humour pharmaco-
kinetic (AHPK) model. Int. J. Antimicrobial Agents, 49, 113-115 (2017).
K. Ogawara, Y. Fukuoka, Y. Yoshizawa, T. Kimura and K. Higaki: Development
of safe and potent oil-in-water emulsion of paclitaxel to treat peritoneal
dissemination. J. Pharm. Sci., 106, 1143-1148 (2017).
D. Tsunashima, K. Yamashita, K. Ogawara, K. Sako, T. Hakomori and K. Higaki:
Development of extended release solid dispersion granules of tacrolimus:
Evaluation of release mechanism and human oral bioavailability: J. Pharm.
Pharmacol., 69, 1697-1706 (2017).
K. Ogawara and K. Higaki: Nanoparticle-based photodynamic theraphy: Current
status and future application to improve outcomes of cancer treatment:
Chem. Pharm. Bull., 65 (7) 637-641 (2017).
K. Ogawara, T. Shiraishi, T. Araki, T. Watanabe, T. Ono and K. Higaki:
Efficient anti-tumor effect of photodynamic treatment with polymeric nanoparticles
composed of polyethylene glycol and polylactic acid block copolymer encapsulating
hydrophobic porphyrin derivative. Eur. J. Pharm. Sci., 82 154-160 (2016).
D. Tsunashima, K. Yamashita, K. Ogawara, K. Sako, and K. Higaki: Preparation
of extended release solid dispersion formulations of tacrolimus using ethylcellulose
and hydroxypropylmethylcellulose by solvent evaporation method. J. Pharm.
Pharmacol., 68 (3) 316-323 (2016).
T. Shehata, T. Kimura, K. Higaki and K. Ogawara: In-vivo disposition characteristics
of PEG niosome and its interaction with serum proteins. Int. J. Pharm.,
512, 322-328 (2016).
H. Kamiguchi, M. Murabayashi, I. Mori, A. Horinouchi and K. Higaki: Biomarker
discovery for drug-induced phospholipidosis: phenylacetylglycine to hippuric
acid ratio in urine and plasma as potential markers. Biomarkers, 22, 178-188
(2016).
T. Araki, K. Ogawara, H. Suzuki, R. Kawai, T. Watanabe, T. Ono and K. Higaki:
Augmented EPR effect by photo-triggered tumor vascular treatment improved
therapeutic efficacy of liposomal paclitaxel in mice bearing tumors with
low permeable vasculature. J. Controlled Rel., 200 (1) 106-114 (2015).
C. Imada, T. Takahashi, M. Kuramoto, K. Masuda, K. Ogawara, A. Sato, Y.
Wataya, H-S. Kim and K. Higaki: Improvement of oral bioavailability of
N-251, a novel antimalarial drug, by increasing lymphatic transport with
long-chain fatty acid-based self-nanoemulsifying drug delivery system.
Pharm. Res., 32 (8) 2595-2608 (2015).
M. Sugihara, S. Takeuchi, M Sugita, K. Higaki, M. Kataoka and S. Yamashita:
Analysis of intra- and inter-subject variability in oral drug absorption
in human bioequivalence studies of 131 generic products. Mol. Pharm., 12
(12) 4405-4413 (2015).
A. Elgaml, K. Higaki and S. Miyoshi: Effects of temperature, growth phase
and luxO-disruption on regulation systems of toxin production in Vibrio
vulnificus strain L-180, a human clinical isolate. World J. Microbiol.
Biotechnol., 30 (2) 681-691 (2014).
M. Naruse, K. Ogawara, T. Kimura, R. Konishi and K. Higaki: Development
of transdermal therapeutic formulation of CNS5161, a novel NMDA receptor
antagonist, by utilizing pressure-sensitive adhesives II: Improved transdermal
absorption and evaluation of efficacy and safety. Eur. J. Pharm. Sci.,
52 86-94 (2014).
H. Tani, S. Hikami, S. Iiduna, M. Yoshimatsu, T. Asama, H. Ota, Y. Kimura,
T. Tatefuji, K. Hashimoto and K. Higaki: Pharmacokinetics and Safety of
Resveratrol Derivatives in Humans after Oral Administration of Melinjo
(Gnetum gnemon L.) Seed Extract Powder. J. Agric. Food Chem., 62 (9) 1999-2007
(2014).
D. Tsunashima, A. Kawamura, M. Murakami, T. Sawamoto, N. Undre, M. Brown,
A. Groenewoud, J. Keirns, J. Holman, A. Connor, H. Wylde, I. Wilding, K.
Ogawara, K. Sako, K. Higaki and R. First: Assessment of Tacrolimus Absorption
from the Human Intestinal Tract: Open Label, Randomized, Four-way Crossover
Study. Clin. Ther., 36 (5) 748-759 (2014).
三宅 正晃、向井 正志、檜垣 和孝: 小腸における難吸収性薬物の吸収改善に関する検討(Absorption Improvement of Poorly
Absorbable Drug from Small Intestine): J. Pharm. Sci. Technol. Japan (薬剤学),
74 (5) 361-365 (2014).
K. Ogawara, S. Abe, K. Un, Y. Yoshizawa, T. Kimura and K. Higaki: Determinants
for in vivo anti-tumor effect of angiogenesis inhibitor SU5416 formulated
in PEGylated emulsion. J. Pharm. Sci., 103 (8) 2464-2469 (2014).
Y. Yoshizawa, K. Ogawara, T. Kimura and K. Higaki: A novel approach to
overcome multidrug resistance: Utilization of P-gp mediated efflux of paclitaxel
to attack neighboring vascular endothelial cells in tumors. Eur. J. Pharm.
Sci., 62 274-280 (2014).
M. Miyake, H. Toguchi, T. Nishibayashi, K. Higaki, A. Sugita, K. Koganei,
N. Kamada, N-T. Kitazume, T. Hisamatsu, T. Sato, S. Okamoto, T. Kanai and
T. Hibi: Establishment of novel prediction system of intestinal absorption
in humans using human intestinal tissues. J. Pharm. Sci., 102 (8) 2564-2571
(2013).
D. Inoue, T. Furubayashi, K. Ogawara, T. Kimura, K. Higaki, T. Shingaki,
S. Kimura, A. Tanaka, H. Katsumi, T. Sakane, A. Yamamoto and Y. Higashi:
In vitro evaluation of the ciliary beat frequency of the rat nasal epithelium
using a high-speed digital imaging system. Biol. Pharm. Bull., 36 (6) 966-973
(2013).
S. Takemura, H. Kondo, S. Watanabe, K. Sako, K. Ogawara and K. Higaki:
Aminoalkylmethacrylate copolymer E improves oral bioavailability of YM466
by suppressing drug – bile Interaction. J. Pharm. Sci., 102 (9) 3128-3135
(2013).
A. Elgaml, K. Higaki and S. Miyoshi: Regulation system of serine protease
production in Vibrio vulnificus strain NCIMB 2137, a metalloprotease-gene
negative strain isolated from a diseased eel. Aquaculture, 416-417 315-321
(2013).
K. Ogawara, Y, Yoshizawa, K. Un T. Araki, T. Kimura and K. Higaki: Nanoparticle-based
passive drug targeting to tumors: Considerations to be given and implications
for further optimization: Biol. Pharm. Bull., 36 (5) 398 – 402 (2013).
M. Naruse, K. Ogawara, T. Kimura, R. Konishi and K. Higaki: Development
of transdermal therapeutic formulation of CNS5161, a novel NMDA receptor
antagonist, by utilizing pressure-sensitive adhesives I. Biol. Pharm. Bull.,
35 (3) 321-328 (2012).
S. Takemura, H. Kondo, K. Suzumura, K. Ogawara, S. Watanabe, K. Sako and
K. Higaki: Evaluation of factors affecting gastrointestinal absorption
of a novel anticoagulant FX-93 for development of oral formulation. J.
Pharm. Sci., 101 (6) 2134-2142 (2012).
D. Inoue, T. Furubayashi, K. Ogawara, T. Kimura, K. Higaki, H. Katsumi,
T. Sakane, A. Yamamoto and Y. Higashi: In vitro evaluation of nasal mucociliary
clearance using excised rat nasal septum. Biol. Pharm. Bull., 35 (6) 889-894
(2012).
T. Araki, Y. Kono, K. Ogawara, T. Watanabe, T. Ono, T. Kimura and K. Higaki:
Formulation and evaluation of paclitaxel-loaded polymeric nanoparticles
composed of polyethylene glycol and polylactic acid block copolymer. Biol.
Pharm. Bull., 35 (8) 1306-1313 (2012).
Y. Miyaji, Y. Kasuya, Y. Furuta, A. Kurihara, M. Takahashi, K. Ogawara,
T. Izumi, O. Okazaki and K. Higaki: Novel comb-shaped PEG modification
enhances the osteoclastic inhibitory effect and bone delivery of osteoprotegerin
after intravenous administration in ovariectomized rats. Pharm. Res., 29
(11) 3143-3155 (2012).
Y. Yoshizawa, K. Ogawara, A. Fushimi, S. Abe, K. Ishikawa,T. Araki, G.
Molema, T. Kimura and K. Higaki: Deeper penetration into tumor tissues
and enhanced in-vivo anti-tumor activity of liposomal paclitaxel by pre-treatment
with angiogenesis inhibitor SU5416. Mol. Pharm., 9 (12) 3486-3494 (2012).
T. Kanda, T. Harada, Y. Tominaga, K. Suzumori, T. Ono, S. Iwabuchi, K.
Ito, K. Ogawara, K. Higaki and Y. Yoshizawa: The Design and evaluation
of emulsion generation device using ultrasonic vibration and microchannel.
Jpn. J. Appl. Phys., 50 07HE24 -1 – 07HE24‐6 (2011).
Y. Yoshizawa, Y. Kono, K. Ogawara, T. Kimura and K. Higaki: PEG liposomalization
of paclitaxel improved its in-vivo disposition and anti-tumor efficacy.
Int. J. Pharm., 412 (1-2) 132-141 (2011).
A. Sato, A. Hiramoto, M. Morita, M. Matsumoto, Y. Komichi, Y. Nakase, N.
Tanigawa, O. Hiraoka, K. Hiramoto, H. Hayatsu, K. Higaki, A. Kawai, A.
Masuyama, M. Nojima, Y. Wataya and H.-S. Kim: Antimalarial activity of
endoperoxide compound 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol.
Parasitol. Int., 60 (3) 270-273 (2011).
N. Kamada, K. Yamada, M. Odomi, T. Mukai, T. Nishibayashi, K. Ogawara,
T. Kimura and K. Higaki: Sex differences in pharmacokinetics of cilostazol
in rats. Xenobiotica, 41 (10) 903-913 (2011).
A. Sato, S. Kawai, A. Hiramoto, M. Morita, N. Tanigawa, Y. Nakase, Y. Komichi,
M. Matsumoto, O. Hiraoka, K. Hiramoto, H. Tokuhara, A. Masuyama, M. Nojima,
K. Higaki, H. Hayatsu, Y. Wataya and H.-S. Kim: Antimalarial activity of
6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) and its carboxylic
acid derivatives. Parasitol. Int., 60 (4) 488-492 (2011).
T. Harada, T. Kanda, O. Suzumori, T. Ono, S. Iwabuchi, K. Ito, K. Ogawara
and K. Higaki: Emusion generating microchannel device oscillated by 2.25
MHz ultrasonic vibrator. Jpn. J. Appl. Phys., 49 07HE13-1 - 07HE13-6 (2010).
檜垣 和孝、木村聰城郎: 自己乳化型マイクロエマルション製剤: J. Pharm. Sci. Technol. Japan. (薬剤学) 70
(1) 32-38 (2010).
T. Hironaka, S. Itokawa, K. Ogawara, K. Higaki and T. Kimura: Quantitative
evaluation of PEPT1 contribution to oral absorption of cephalexin in rats.
Pharm. Res., 26 (1) 40-50 (2009).
K. Ogawara, K. Un, K. Tanaka, K. Higaki and T. Kimura: In vivo anti-tumor
effect of PEG liposomal doxorubicin (DOX) in DOX-resistant tumor-bearing
mice: Involvement of cytotoxic effect on vascular endothelial cells. J.
Controlled Rel., 133 (1) 4-10 (2009).
F. Mukaizawa, K. Taniguchi, M. Miyake, K. Ogawara, M. Odomi, K. Higaki
and T. Kimura: Novel oral absorption system containing polyamines and bile
salts enhances drug transport via both transcellular and paracellular pathways
across Caco-2 cell monolayers. Int. J. Pharm., 367 (1-2) 103-108 (2009).
T. Kimoto, M. Takanashi, H. Mukai, K. Ogawara, T. Kimura and K. Higaki:
Effect of adrenergic stimulation on drug absorption via passive diffusion
in Caco-2 cells. Int. J. Pharm., 368 (1-2) 31-36 (2009).
C. Takayama, F. Mukaizawa, T. Fujita, K. Ogawara, K. Higaki and T. Kimura:
Amino acids suppress apoptosis induced by sodium laurate, an absorption
enhancer. J. Pharm. Sci., 98 (12) 4629-4638 (2009).
檜垣 和孝: オーラルメディケーションにおける胃排出の重要性: Pharm Tech Japan 25 (13) 48-52 (2009).
檜垣 和孝: 自己乳化型マイクロエマルション製剤による吸収改善: Farumashia 45 (12) 1213-1216 (2009).
J. Yokoe, S. Sakuragi, K. Yamamoto, T. Teragaki, K. Ogawara, K. Higaki,
N. Katayama, T. Kai, M. Sato and T. Kimura: Albumin-conjugated PEG liposome
enhances tumor distribution of liposomal doxorubicin in rats. Int. J. Pharm.,
353 (1-2) 28-34 (2008).
M. Ishii, Y. Kawakami, H. Date, K. Higaki, T. Sendo and T. Kimura: Correlation
of cyclosporine blood concentration-dose ratio and biochemical parameters
in living-donor lung transplant patients. Jpn. J. Pharm. Healthcare Sci.,
34 (4) 381-385 (2008).
H. Wakamatsu, S. Nagamachi, R. Nishii, K. Higaki, K. Kawai, K. Kamimura,
S. Fujita, S. Futami and S. Tamura: Effect of percutaneous endoscopic gastrostomy
on gastrointestinal motility: evaluation by gastric-emptying scintigraphy.
Nucl. Med. Commun., 29 (6) 562-567 (2008).
K. Higaki, S. Y. Choe, R. Löbenberg, L. S. Welage and G. L. Amidon: Mechanistic
understanding of time-dependent oral absorption based on gastric motor
activity in humans. Eur. J. Pharm. Biopharm., 70 (1) 313-325 (2008).
K. Ogawara, K. Un, K. Minato, K. Tanaka, K. Higaki and T. Kimura: Determinants
for in-vivo anti-tumor effects of PEG liposomal doxorubicin: Importance
of vascular permeability within tumors. Int. J. Pharm., 359 (1-2) 234-240
(2008).
T. Shehata, K. Ogawara, K. Higaki and T. Kimura: Prolongation of residence
time of liposome by surface-modification with mixture of hydrophilic polymers.
Int. J. Pharm., 359 (1-2) 272-279 (2008).
J. Jinno, N. Kamada, M. Miyake, K. Yamada, T. Mukai, M. Odomi, H. Toguchi,
G. G. Liversidge, K. Higaki and T. Kimura: In vitro-in vivo correlation
for wet-milled tablet of poorly water-soluble cilostazol. J. Controlled
Rel., 130 (1) 29-37 (2008).
Y. Metsugi, Y. Miyaji, K. Ogawara, K. Higaki and T. Kimura: Appearance
of double peaks in plasma concentration – time profile after oral administration
depends on gastric emptying profile and weight function. Pharm. Res., 25
(4) 886-895 (2008).
Y. Fujioka, Y. Metsugi, K. Ogawara, K. Higaki and T. Kimura: Evaluation
of in-vivo dissolution behavior and GI transit of griseofulvin, a BCS class
II drug. Int. J. Pharm., 352 (1-2) 36-43 (2008).
K. Furumoto, J. Yokoe, K. Ogawara, S. Amano, M. Takaguchi, K. Higaki, T.
Kai and T. Kimura: Effect of coupling of albumin onto surface of PEG liposome
on its in-vivo disposition. Int. J. Pharm., 329 (1-2) 110-116 (2007).
S. Nagayama, K. Ogawara, K. Minato, Y. Fukuoka, Y. Takakura, M. Hashida,
K. Higaki and T. Kimura: Fetuin mediates hepatic uptake of negatively charged
nanoparticles via scavenger receptor. Int. J. Pharm., 329 (1-2) 192-198
(2007).
N. Nagahara, Y. Akiyama, K. Higaki and T. Kimura: Animal models for predicting
potency of oral sustained-release adhesive microspheres in humans. Int.
J. Pharm., 331 (1) 46-53 (2007).
Y. Fujioka, K. Kadono, Y. Fujie, Y. Metsugi, K. Ogawara, K. Higaki and
T. Kimura: Prediction of oral absorption of griseofulvin, a BCS class II
drug, based on GITA model: Utilization of a more suitable medium for in-vitro
dissolution study. J. Controlled Rel., 119 (2) 222-228 (2007).
S. Nagayama, K. Ogawara, Y. Fukuoka, K. Higaki and T. Kimura: Time-dependent
changes in opsonins amount associated on nanoparticles alter their hepatic
characteristics. Int. J. Pharm., 342 (1-2) 215-221 (2007).
檜垣 和孝: アミノ酸とラウリン酸を利用した安全性の高い吸収改善製剤の開発: アミノ酸によるcytoprotectionとその機構 (Safe
improvement of drug absorption by combinatorial use of sodium laurate with
amino acids: Cytoprotection by amino acids and its mechanisms). 薬学雑誌 (Journal
of the Pharmaceutical Society of Japan) 127 (4) 589-599 (2007).
M. Miyake, T. Minami, M. Hirota, H. Toguchi, M. Odomi, K. Ogawara, K. Higaki
and T. Kimura: Novel oral formulation safely improving intestinal absorption
of poorly absorbable drugs: Utilization of polyamines and bile acids. J.
Controlled Rel., 111 (1-2) 27-34 (2006).
J. Jinno, N. Kamada, M. Miyake, K. Yamada, T. Mukai, M. Odomi, H. Toguchi,
G. G. Liversidge, K. Higaki and T. Kimura: Effect of particle size reduction
on dissolution and oral absorption of a poorly water-soluble drug, cilostazol,
in beagle dogs. J. Controlled Rel., 111 (1-2) 56-64 (2006).
M. Miyake, T. Minami, Y. Oka, N. Kamada, H. Yamazaki, Y. Kato, T. Mukai,
H. Toguchi, M. Odomi, K. Ogawara, K. Higaki and T. Kimura: Optimization
of suppository preparation containing sodium laurate and taurine that can
safely improve rectal absorption of rebamipide. Biol. Pharm. Bull., 29
(2) 330-335 (2006).
N. Tanaka, K. Imai, K. Okimoto, S. Ueda, Y. Tokunaga, R. Ibuki, K. Higaki
and T. Kimura: Development of novel sustained-release system, disintegration-controlled
matrix tablet (DCMT) with solid dispersion granules of nilvadipine (II):
in vivo evaluation. J. Controlled Rel., 112 (1) 51-56 (2006).
T. Okuda, K. Kadotsuji, C. Takayama, K. Hanada, F. Mukaizawa, K. Ogawara,
K. Higaki and T. Kimura: Involvement of intracellular Ca2+ dynamics in
cytoprotective action by amino acids and cytotoxicity by sodium laurate,
an absorption enhancer. J. Pharm. Sci., 95 (10) 2256-2265 (2006).
M. Miyake, T. Minami, H. Toguchi, M. Odomi, K. Ogawara, K. Higaki and T.
Kimura: Importance of bile acids for novel oral absorption system containing
polyamines to improve intestinal absorption. J. Controlled Rel., 115 (2)
130-133 (2006).
N. Tanaka, K. Imai, K. Okimoto, S. Ueda, Y. Tokunaga, A. Ohike, R. Ibuki,
K. Higaki and T. Kimura: Development of novel sustained-release system,
disintegration-controlled matrix tablet (DCMT) with solid dispersion granules
of nilvadipine. J. Controlled Rel., 108 (2-3) 386-395 (2005).
K. Higaki, K. Nakayama, T. Suyama, C. Amnuaikit, K. Ogawara and T. Kimura:
Enhancement of topical delivery of drugs via direct penetration by reducing
blood flow rate in skin. Int. J. Pharm., 288 (2), 227-233 (2005).
H. Hiraoka, N. Kimura, Y. Furukawa, K. Ogawara, T. Kimura and K. Higaki:
Upregulation of P-glycoprotein expression in small intestine under chronic
serotonin-depleted conditions in rats. J. Pharmacol. Exp. Ther., 312 (1),
248-255 (2005).
C. Amnuaikit, I. Ikeuchi, K. Ogawara, K. Higaki and T. Kimura: Skin permeation
of propranolol from polymeric film containing terpene enhancers for transdermal
use. Int. J. Pharm., 289 (1-2), 167-178 (2005).
T. Takatori, K. Yamamoto, T. Yamaguchi, K. Higaki and T. Kimura: Design
of controlled-release morphine suppositories containing polyglycerol ester
of fatty acid. Biol. Pharm. Bull., 28 (8) 1480-1484 (2005).
K. Furumoto, S. Nagayama, K. Ogawara, Y. Takakura, M. Hashida, K. Higaki
and T. Kimura: Hepatic uptake of negatively charged particles in rats:
Possible involvement of serum proteins in recognition by scavenger receptor.
J. Controlled Rel., 97 (1), 133-141 (2004).
C. Nishida, K. Ogawara, T. Kimura and K. Higaki: Pharmacokinetic analysis
of factors determining elimination pathways for sulfate and glucuronide
metabolites of xenobiotics III: Mechanisms for sinusoidal efflux of 4-methylumbelliferone
sulfate. Xenobiotica, 34 (5) 439-448 (2004).
K. Higaki, M. Sone, K. Ogawara and T. Kimura: Regulation of drug absorption
from small intestine by enteric nervous system I: a poorly absorbable drug
via passive diffusion. Drug Metab. Pharmacokinet., 19 (3) 198-205 (2004).
T. Takatori, N. Shimono, K. Higaki and T. Kimura: Evaluation of sustained
release suppositories prepared with fatty base including solid fats with
high melting points. Int. J. Pharm., 278 (2), 275-282 (2004).
M. Miyake, N. Kamada, Y. Oka, T. Mukai, T. Minami, H. Toguchi, M. Odomi,
K. Ogawara, K. Higaki and T. Kimura: Development of suppository formulation
safely improving rectal absorption of rebamipide, a poorly absorbable drug,
by utilizing sodium laurate and Taurine. J. Controlled Rel., 99 (1), 63-71
(2004).
K. Ogawara, K. Furumoto, S. Nagayama, K. Minato, K. Higaki, T. Kai and
T. Kimura: Pre-coating with serum albumin reduces receptor-mediated hepatic
disposition of polystyrene nanosphere: Implications for rational design
of nanoparticles. J. Controlled Rel., 100 (3), 451-455 (2004).
J. Yokoe, N, Iwasaki, S. Haruta, K. Kadono, K. Ogawara, K. Higaki and T.
Kimura: Analysis and prediction of absorption behavior of colon-targeted
prodrug in rats by Gastrointestinal-Transit-Absorption (GITA) model. J.
Controlled Rel., 86 (2-3) 305-313 (2003).
K. Nezasa, K. Higaki, M. Takeuchi, M. Nakano and M. Koike: Uptake of rosuvastatin
by isolated rat hepatocytes: Comparison with pravastatin. Xenobiotica,
33 (4) 379-388 (2003).
M. Miyake, Y. Oka, T. Minami, H. Toguchi, M. Odomi, K. Ogawara, K. Higaki
and T. Kimura: Combinatorial use of sodium laurate with taurine or L-glutamine
enhances colonic absorption of rebamipide, poorly absorbable anti-ulcer
drug, without any serious histopathological mucosal damage. J. Pharm. Sci.,
92 (4) 911-921 (2003).
S. Ohtani, K. Shirasu, K. Ogawara, K. Higaki and T. Kimura: Evaluation
of inhibitory activity of casein on proteases in rat intestine. Pharm.
Res., 20 (4) 611-617 (2003).
Y-Y Chiu, K. Higaki, B. L. Neudeck, J. L. Barnett, L. S. Welage and G.
L. Amidon: Human jejunal permeability of cyclosporin A: Influence of surfactants
on P-glycoprotein efflux in Caco-2 cells. Pharm. Res., 20 (5) 749-756 (2003).
S. Ohtani, K Ogawara, K. Higaki and T. Kimura: Casein enhances stability
of peptides in intestinal lumen: Role of digested products of casein. Pharm.
Res., 20 (11) 1746-1751 (2003).
K. Yamashita, T. Nakate, K. Okimoto, A. Ohike, Y. Tokunaga, R. Ibuki, K.
Higaki and T. Kimura: Establishment of new preparation method for solid
dispersion formulation of tacrolimus. Int. J. Pharm., 267 (1-2), 79-91
(2003).
K. Higaki, M. Ishii, H. Esumi, M. Kanayama, K. Ogawara and T. Kimura: Pharmacokinetic
analysis of factors determining elimination pathways for sulfate and glucuronide
Metabolites of xenobiotics II: Studies with isolated perfused rat liver.
Xenobiotica, 33 (11) 1097-1108 (2003).
K. Higaki, C. Amnuaikit and T. Kimura: Strategies for overcoming stratum
corneum: Chemical and Physical Approaches. Am. J. Drug Deliv., 1 (3) 187-214
(2003).
T. Kimura, H. Yamano, A. Tanaka, T. Matsumura, M. Ueda, K. Ogawara and
K. Higaki: Transport of D-glucose across cultured stratified cell layer
of human oral mucosal cells. J. Pharm. Pharmacol., 54 (2) 213-219 (2002).
Y. Endo, K. Hanada, M. Miyake, K. Ogawara, K. Higaki and T. Kimura: Mechanisms
of cytoprotective effect of amino acids on local toxicity caused by sodium
laurate, a drug absorption enhancer, in intestinal epithelium. J. Pharm.
Sci., 91 (3) 730-743 (2002).
S. Haruta, K. Kawai, R. Nishii, S. Jinnouchi, K. Ogawara, K. Higaki, S.
Tamura, K. Arimori and T. Kimura: Prediction of plasma concentration -
time curve of orally administered theophylline based on a scintigraphic
monitoring of gastrointestinal transit in human volunteers. Int. J. Pharm.,
233 (1-2) 179-190 (2002).
M. Ishii, M. Kanayama, H. Esumi, K. Ogawara, T. Kimura and K. Higaki: Pharmacokinetic
analysis of factors determining elimination pathways for sulfate and glucuronide
metabolites of drugs I: Studies by in vivo constant infusion. Xenobiotica,
32 (5), 441-450 (2002).
K. Higaki, M. Asai, T. Suyama, K. Nakayama, K. Ogawara and T. Kimura: Estimation
of intradermal disposition kinetics of drugs: II. Factors determining penetration
of drugs from viable skin to muscular layer. Int. J. Pharm., 239 (1-2),
129-141 (2002).
J. Kubo, Y. Ohigashi, M. Hamabe, K. Ogawara, K. Higaki, H. Saito and T.
Kimura: Pharmacokinetic evaluation of high pulmonary disposition of clarithromycin
after systemic administration. Xenobiotica, 32 (10), 879-893 (2002).
K. Furumoto, K. Ogawara, S. Nagayama, Y. Takakura, M. Hashida, K. Higaki
and T. Kimura: Important role of serum proteins associated on the surface
of particles in their hepatic disposition. J. Controlled Rel., 83 (1),
89-96 (2002).
K. Kadono, J. Yokoe, K. Ogawara, K. Higaki and T. Kimura: Analysis and
prediction of absorption behavior for theophylline orally administered
as powders based on gastrointestinal-transit-absorption (GITA) model. Drug
Metab. Pharmacokinet., 17 (4), 307-315 (2002).
K. Nezasa, K. Higaki, T. Matsumura, K. Inazawa, H. Hasegawa, M. Nakano
and M. Koike: Liver-specific distribution of rosuvastatin in rats: Comparison
with pravastatin and simvastatin. Drug Metab. Dispos., 30 (11) 1158-1163
(2002).
T. Kimura and K. Higaki: Gastrointestinal transit and drug absorption.
Biol. Pharm. Bull., 25 (2) 149-164 (2002).
S. Haruta, K. Kawai, S. Jinnouchi, K. Ogawara, K. Higaki, S. Tamura, K.
Arimori and T. Kimura: Evaluation of absorption kinetics of orally administered
theophylline in rats based on gastrointestinal transit monitoring by gamma
scintigraphy. J. Pharm. Sci., 90 (4) 464-473 (2001).
K. Higaki, S. Yamashita and G. L. Amidon: Time-dependent oral absorption
models. J. Pharmacokin. Pharmacodyn., 28 (2) 109-128 (2001).
X-Y. Chu, G. P. S-Castaňo, K. Higaki, O. D-Man, C-P. Hsu and G. L. Amidon:
Correlation between epithelial cell permeability of cephalexin and expression
of intestinal oligopeptide transporter. J. Pharmacol. Exp. Ther., 299 (2)
575-582 (2001).
K. Furumoto, K. Ogawara, M. Yoshida, Y. Takakura, M. Hashida, K. Higaki
and T. Kimura: Biliary excretion of polystyrene microspheres depends on
the type of receptor-mediated uptake in rat liver. Biochim. Biophys. Acta.,
1526 (2) 221-226 (2001).
T. Yata, Y. Endo, M. Sone, K. Ogawara, K. Higaki and T. Kimura: Amino acids
protect epithelial cells from local toxicity by absorption enhancer, sodium
laurate. J. Pharm. Sci., 90 (8) 1456-1465 (2001).
K. Higaki, T. Yata, M. Sone, K. Ogawara and T. Kimura: Estimation of absorption
enhancement by medium-chain fatty acids in rat large intestine. Res. Commun.
Mol. Pathol. Pharmacol., 109 (3-4) 231-240 (2001).
K. Ogawara, K. Furumoto, Y. Takakura, M. Hashida, K. Higaki and T. Kimura:
Surface hydrophobicity is not necessarily the most important determinant
in their in vivo disposition after intravenous administration in rats.
J. Controlled Release, 77 (3) 191-198 (2001)
大河原賢一、檜垣 和孝、木村聰城郎: 微粒子キャリアを用いたデリバリーと動態解析. Drug Delivery System 16 (5) 395-400
(2001).
T. Kimura, N. Iwasaki, J. Yokoe, S. Haruta, Y. Yokoo, K. Ogawara and K.
Higaki: Analysis and prediction of absorption profile including hepatic
first-pass metabolism of N-methyltyramine, a potent stimulant of gastrin
release present in beer, after oral ingestion in rats by gastrointestinal-transit-absorption
model. Drug Metab. Dispos., 28 (5) 577-581 (2000).
C.W. Botka, T. W. Wittig, R. C. Graul, C. U. Nielsen, K. Higaki, G. L.
Amidon and W. Sadee: Human proton/oligopeptide transporter (POT) genes:
Identification of putative human genes using bioinformatics. AAPS J., 2
(2) issue 16 (2000).
K. Nakayama, H. Matsuura, M. Asai, K. Ogawara, K. Higaki and T. Kimura:
Estimation of intradermal disposition kinetics of drugs (I): Analysis by
compartment model with contralateral tissues. Pharm. Res., 16 (2) 302-308
(1999).
K. Ogawara, M. Yoshida, K. Higaki, T. Kimura, K. Shiraishi, M. Nishikawa,
Y. Takakura and M. Hashida: Hepatic uptake of polystyrene microspheres
in rats: effect of particle size on intrahepatic distribution, J. Controlled
Release, 59 (1) 15-22 (1999).
Y. Oyama, H. Yamano, A. Ohkuma, K. Ogawara, K. Higaki and T. Kimura: Carrier-mediated
transport systems for glucose in mucosal cells of human oral cavity. J.
Pharm. Sci., 88 (8) 830-834 (1999).
K. Ogawara, M. Yoshida, J. Kubo, M. Nishikawa, Y. Takakura, M. Hashida,
K. Higaki, and T. Kimura: Mechanisms of hepatic disposition of polystyrene
microspheres in rats: Effects of serum depend on the sizes of microspheres.
J. Controlled Release, 61 (3) 241-250 (1999).
K. Ogawara, M. Yoshida, Y. Takakura, M. Hashida, K. Higaki and T. Kimura:
Interaction of polystyrene microspheres with liver cells: Roles of membrane
receptors and serum proteins. Biochim. Biophys. Acta, 1472 (1-2) 165-172
(1999).
K. Ogawara, M. Yoshida, K. Furumoto, Y. Takakura, M. Hashida, K. Higaki
and T. Kimura: Uptake by hepatocytes and biliary excretion of intravenously
administered polystyrene microsphere in rats. J. Drug Targeting, 7 (3)
213-221 (1999).
K. Higaki, T. Yukawa, M. Takeuchi, K. Nezasa and M. Nakano: Stereoselective
uptake of an organic anion across the renal basolateral membrane in isolated
perfused rat kidney. Drug Metab. Dispos., 26 (2) 138-145 (1998).
Y. Emi, D. Tsunashima, K. Ogawara, K. Higaki and T. Kimura: Role of P-glycoprotein
as a secretory mechanism in quinidine absorption from rat small intestine.
J. Pharm. Sci., 87 (3) 295-299 (1998).
K. Nezasa, K. Higaki, M. Takeuchi, T. Yukawa and M. Nakano: Pharmacokinetics
of a novel benzodiazepine partial inverse agonist in the F344 rat, SD rat
and B6C3F1 mouse. Xenobiotica, 28 (5) 515-525 (1998).
S. Haruta, N. Iwasaki, K. Ogawara, K. Higaki and T. Kimura: Absorption
behavior of orally administered drugs in rats treated with propantheline.
J. Pharm. Sci., 87 (9) 1081-1085 (1998).
S. Yagi, K. Nakayama, Y. Kurosaki, K. Higaki and T. Kimura: Factors determining
drug residence in skin during transdermal absorption. Biol. Pharm. Bull.,
21 (11) 1195-1201 (1998).
K. Sugimoto, M. Yoshida, T. Yata, K. Higaki and T. Kimura: Evaluation of
poly(vinyl alcohol)-gel spheres containing chitosan as dosage form to control
gastrointestinal transit time of drugs. Biol. Pharm. Bull., 21 (11) 1202-1206
(1998).
T. Sawamoto, S. Haruta, Y. Kurosaki, K. Higaki and T. Kimura: Prediction
of plasma concentration profile of orally administered drugs based on gastrointestinal
transit kinetics and absorbability in rats. J. Pharm. Pharmacol., 49 (1)
450-457 (1997).
K. Higaki, Y. Matsumoto, R. Fujimoto, Y. Kurosaki and T. Kimura: Developmental
changes in pharmacokinetics of recombinant human insulin-like growth factor-I
in rats. Res. Commun. Mol. Pathol. Pharmacol., 97 (2) 115-124 (1997).
T. Kimura, Y. Murakawa, M. Ohno, S. Ohtani and K. Higaki: Gastrointestinal
absorption of recombinant human insulin-like growth factor-I in rats. J.
Pharmacol. Exp. Ther., 283 (2) 611-618 (1997).
K. Higaki, Y. Matsumoto, R. Fujimoto, Y. Kurosaki and T. Kimura: Pharmacokinetics
of recombinant human insulin-like growth factor-I in diabetic rats. Drug
Metab. Dispos., 25 (11) 1324-1327 (1997).
K. Higaki, M. Takeuchi and M. Nakano: Estimation and enhancement of in
vitro corneal transport of S-1033, a novel antiglaucoma medication. Int.
J. Pharm., 132 (1-2) 165-173 (1996).
K. Higaki: Stereoselective pharmacokinetics of a chiral organic anion in
rats: analysis of its kinetics in liver and kidney. Ann. Rev. Shionogi
Res. Lab., 46, 48-85 (1996)