Loading…
Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann–Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease
Niemann–Pick type C disease (NPC), an autosomal recessive lysosomal storage disorder, is an inherited disease characterized by the accumulation of intracellular unesterified cholesterol. A solubilizing agent of lipophilic compounds, 2-hydroxypropyl-β-cyclodextrin (HPBCD), is an attractive drug candi...
Saved in:
Published in: | Biological & pharmaceutical bulletin 2015/06/01, Vol.38(6), pp.844-851 |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | cdi_FETCH-LOGICAL-c416t-d4a188198ca002ca0db628f2557d29ae176660fb9dde4cf59acf0a6eb627ca903 |
---|---|
cites | cdi_FETCH-LOGICAL-c416t-d4a188198ca002ca0db628f2557d29ae176660fb9dde4cf59acf0a6eb627ca903 |
container_end_page | 851 |
container_issue | 6 |
container_start_page | 844 |
container_title | Biological & pharmaceutical bulletin |
container_volume | 38 |
creator | Tanaka, Yuta Yamada, Yusei Ishitsuka, Yoichi Matsuo, Muneaki Shiraishi, Koki Wada, Koki Uchio, Yushiro Kondo, Yuki Takeo, Toru Nakagata, Naomi Higashi, Taishi Motoyama, Keiichi Arima, Hidetoshi Mochinaga, Sakiko Higaki, Katsumi Ohno, Kousaku Irie, Tetsumi |
description | Niemann–Pick type C disease (NPC), an autosomal recessive lysosomal storage disorder, is an inherited disease characterized by the accumulation of intracellular unesterified cholesterol. A solubilizing agent of lipophilic compounds, 2-hydroxypropyl-β-cyclodextrin (HPBCD), is an attractive drug candidate against NPC disease. However, establishment of the optimum dosage of HPBCD remains to be determined. In this study, we evaluated the effective dosage of HPBCD in NPC model (Npc1−/−) mice, and determined serum HPBCD concentrations. Subcutaneous injection of 1000–4000 mg/kg HPBCD improved the lifespan of Npc1−/− mice. In addition, liver injury and cholesterol sequestration were significantly prevented by 4000 mg/kg HPBCD in Npc1−/− mice. Serum HPBCD concentrations, when treated at the effective dosages (1000–4000 mg/kg), were approximately 1200–2500 µg/mL at 0.5 h after subcutaneous injection, and blood HPBCD concentrations were immediately eliminated in Npc1−/− mice. Furthermore, we examined serum HPBCD concentrations when treated at 40000 mg (approximately 2500 mg/kg) in a patient with NPC. We observed that the effective concentration in the in vivo study using Npc1−/− mice was similar to that in the patient. In the patient, systemic clearance and the volume of distribution of HPBCD were in accordance with the glomerular filtration rate and extracellular fluid volume, respectively. These results could provide useful information for developing the optimal dosage regimen for HPBCD therapy when administered intravenously to NPC patients. |
doi_str_mv | 10.1248/bpb.b14-00726 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1685749257</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1685749257</sourcerecordid><originalsourceid>FETCH-LOGICAL-c416t-d4a188198ca002ca0db628f2557d29ae176660fb9dde4cf59acf0a6eb627ca903</originalsourceid><addsrcrecordid>eNo9kcFu1DAQhi1ERZeWI1fkIxcX20kc51gthVZq6R7aszVxJqzbxAmxV21uvAMSD8KD8BA8Cd5uu5I1PsynT5r_J-S94CdC5vpTPdYntcgZ56VUr8hCZHnJCimK12TBK6GZEoU-JG9DuOOJ4TJ7Qw6l4rLUMl-Q32dt6yzYmQ4tlex8bqbhcR6nYZw79vcPs7PthgYf4-Q8Te-bwx68__fz18rZe_rZBYSA9GYekS7pVUI7euUsUvANvYiBrtYw9WCHe-cxOktPPXRzcGErA7qC6NBH-uDimsY1vgiPyUELXcB3z_8Ruf1ydrM8Z5fXXy-Wp5fM5kJF1uQgtBaVtsC5TKOpldStLIqykRWgKJVSvK2rpsHctkUFtuWgMFGlhYpnR-Tjzpsu_rHBEE3vgsWuA4_DJhihdFHmlSzKhLIdaqchhAlbM06uh2k2gpttFSZVYVIV5qmKxH94Vm_qHps9_ZJ9ApY74C5E-I57AKaUU4dPukwbtR177X5rU64GffYfMtigMw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1685749257</pqid></control><display><type>article</type><title>Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann–Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease</title><source>Free Full-Text Journals in Chemistry</source><creator>Tanaka, Yuta ; Yamada, Yusei ; Ishitsuka, Yoichi ; Matsuo, Muneaki ; Shiraishi, Koki ; Wada, Koki ; Uchio, Yushiro ; Kondo, Yuki ; Takeo, Toru ; Nakagata, Naomi ; Higashi, Taishi ; Motoyama, Keiichi ; Arima, Hidetoshi ; Mochinaga, Sakiko ; Higaki, Katsumi ; Ohno, Kousaku ; Irie, Tetsumi</creator><creatorcontrib>Tanaka, Yuta ; Yamada, Yusei ; Ishitsuka, Yoichi ; Matsuo, Muneaki ; Shiraishi, Koki ; Wada, Koki ; Uchio, Yushiro ; Kondo, Yuki ; Takeo, Toru ; Nakagata, Naomi ; Higashi, Taishi ; Motoyama, Keiichi ; Arima, Hidetoshi ; Mochinaga, Sakiko ; Higaki, Katsumi ; Ohno, Kousaku ; Irie, Tetsumi</creatorcontrib><description>Niemann–Pick type C disease (NPC), an autosomal recessive lysosomal storage disorder, is an inherited disease characterized by the accumulation of intracellular unesterified cholesterol. A solubilizing agent of lipophilic compounds, 2-hydroxypropyl-β-cyclodextrin (HPBCD), is an attractive drug candidate against NPC disease. However, establishment of the optimum dosage of HPBCD remains to be determined. In this study, we evaluated the effective dosage of HPBCD in NPC model (Npc1−/−) mice, and determined serum HPBCD concentrations. Subcutaneous injection of 1000–4000 mg/kg HPBCD improved the lifespan of Npc1−/− mice. In addition, liver injury and cholesterol sequestration were significantly prevented by 4000 mg/kg HPBCD in Npc1−/− mice. Serum HPBCD concentrations, when treated at the effective dosages (1000–4000 mg/kg), were approximately 1200–2500 µg/mL at 0.5 h after subcutaneous injection, and blood HPBCD concentrations were immediately eliminated in Npc1−/− mice. Furthermore, we examined serum HPBCD concentrations when treated at 40000 mg (approximately 2500 mg/kg) in a patient with NPC. We observed that the effective concentration in the in vivo study using Npc1−/− mice was similar to that in the patient. In the patient, systemic clearance and the volume of distribution of HPBCD were in accordance with the glomerular filtration rate and extracellular fluid volume, respectively. These results could provide useful information for developing the optimal dosage regimen for HPBCD therapy when administered intravenously to NPC patients.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.b14-00726</identifier><identifier>PMID: 26027824</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>2-Hydroxypropyl-beta-cyclodextrin ; 2-hydroxypropyl-β-cyclodextrin ; Animals ; beta-Cyclodextrins - administration & dosage ; beta-Cyclodextrins - blood ; beta-Cyclodextrins - pharmacokinetics ; beta-Cyclodextrins - therapeutic use ; Cholesterol - metabolism ; Disease Models, Animal ; Humans ; Liver - drug effects ; Liver - metabolism ; Liver Diseases - etiology ; Liver Diseases - metabolism ; Liver Diseases - prevention & control ; Male ; Mice ; Mice, Knockout ; Niemann-Pick Disease, Type C - complications ; Niemann-Pick Disease, Type C - drug therapy ; Niemann–Pick type C ; Npc1-deficient mouse ; Proteins - genetics ; Solubility</subject><ispartof>Biological and Pharmaceutical Bulletin, 2015/06/01, Vol.38(6), pp.844-851</ispartof><rights>2015 The Pharmaceutical Society of Japan</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-d4a188198ca002ca0db628f2557d29ae176660fb9dde4cf59acf0a6eb627ca903</citedby><cites>FETCH-LOGICAL-c416t-d4a188198ca002ca0db628f2557d29ae176660fb9dde4cf59acf0a6eb627ca903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26027824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tanaka, Yuta</creatorcontrib><creatorcontrib>Yamada, Yusei</creatorcontrib><creatorcontrib>Ishitsuka, Yoichi</creatorcontrib><creatorcontrib>Matsuo, Muneaki</creatorcontrib><creatorcontrib>Shiraishi, Koki</creatorcontrib><creatorcontrib>Wada, Koki</creatorcontrib><creatorcontrib>Uchio, Yushiro</creatorcontrib><creatorcontrib>Kondo, Yuki</creatorcontrib><creatorcontrib>Takeo, Toru</creatorcontrib><creatorcontrib>Nakagata, Naomi</creatorcontrib><creatorcontrib>Higashi, Taishi</creatorcontrib><creatorcontrib>Motoyama, Keiichi</creatorcontrib><creatorcontrib>Arima, Hidetoshi</creatorcontrib><creatorcontrib>Mochinaga, Sakiko</creatorcontrib><creatorcontrib>Higaki, Katsumi</creatorcontrib><creatorcontrib>Ohno, Kousaku</creatorcontrib><creatorcontrib>Irie, Tetsumi</creatorcontrib><title>Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann–Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Niemann–Pick type C disease (NPC), an autosomal recessive lysosomal storage disorder, is an inherited disease characterized by the accumulation of intracellular unesterified cholesterol. A solubilizing agent of lipophilic compounds, 2-hydroxypropyl-β-cyclodextrin (HPBCD), is an attractive drug candidate against NPC disease. However, establishment of the optimum dosage of HPBCD remains to be determined. In this study, we evaluated the effective dosage of HPBCD in NPC model (Npc1−/−) mice, and determined serum HPBCD concentrations. Subcutaneous injection of 1000–4000 mg/kg HPBCD improved the lifespan of Npc1−/− mice. In addition, liver injury and cholesterol sequestration were significantly prevented by 4000 mg/kg HPBCD in Npc1−/− mice. Serum HPBCD concentrations, when treated at the effective dosages (1000–4000 mg/kg), were approximately 1200–2500 µg/mL at 0.5 h after subcutaneous injection, and blood HPBCD concentrations were immediately eliminated in Npc1−/− mice. Furthermore, we examined serum HPBCD concentrations when treated at 40000 mg (approximately 2500 mg/kg) in a patient with NPC. We observed that the effective concentration in the in vivo study using Npc1−/− mice was similar to that in the patient. In the patient, systemic clearance and the volume of distribution of HPBCD were in accordance with the glomerular filtration rate and extracellular fluid volume, respectively. These results could provide useful information for developing the optimal dosage regimen for HPBCD therapy when administered intravenously to NPC patients.</description><subject>2-Hydroxypropyl-beta-cyclodextrin</subject><subject>2-hydroxypropyl-β-cyclodextrin</subject><subject>Animals</subject><subject>beta-Cyclodextrins - administration & dosage</subject><subject>beta-Cyclodextrins - blood</subject><subject>beta-Cyclodextrins - pharmacokinetics</subject><subject>beta-Cyclodextrins - therapeutic use</subject><subject>Cholesterol - metabolism</subject><subject>Disease Models, Animal</subject><subject>Humans</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver Diseases - etiology</subject><subject>Liver Diseases - metabolism</subject><subject>Liver Diseases - prevention & control</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Niemann-Pick Disease, Type C - complications</subject><subject>Niemann-Pick Disease, Type C - drug therapy</subject><subject>Niemann–Pick type C</subject><subject>Npc1-deficient mouse</subject><subject>Proteins - genetics</subject><subject>Solubility</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNo9kcFu1DAQhi1ERZeWI1fkIxcX20kc51gthVZq6R7aszVxJqzbxAmxV21uvAMSD8KD8BA8Cd5uu5I1PsynT5r_J-S94CdC5vpTPdYntcgZ56VUr8hCZHnJCimK12TBK6GZEoU-JG9DuOOJ4TJ7Qw6l4rLUMl-Q32dt6yzYmQ4tlex8bqbhcR6nYZw79vcPs7PthgYf4-Q8Te-bwx68__fz18rZe_rZBYSA9GYekS7pVUI7euUsUvANvYiBrtYw9WCHe-cxOktPPXRzcGErA7qC6NBH-uDimsY1vgiPyUELXcB3z_8Ruf1ydrM8Z5fXXy-Wp5fM5kJF1uQgtBaVtsC5TKOpldStLIqykRWgKJVSvK2rpsHctkUFtuWgMFGlhYpnR-Tjzpsu_rHBEE3vgsWuA4_DJhihdFHmlSzKhLIdaqchhAlbM06uh2k2gpttFSZVYVIV5qmKxH94Vm_qHps9_ZJ9ApY74C5E-I57AKaUU4dPukwbtR177X5rU64GffYfMtigMw</recordid><startdate>20150601</startdate><enddate>20150601</enddate><creator>Tanaka, Yuta</creator><creator>Yamada, Yusei</creator><creator>Ishitsuka, Yoichi</creator><creator>Matsuo, Muneaki</creator><creator>Shiraishi, Koki</creator><creator>Wada, Koki</creator><creator>Uchio, Yushiro</creator><creator>Kondo, Yuki</creator><creator>Takeo, Toru</creator><creator>Nakagata, Naomi</creator><creator>Higashi, Taishi</creator><creator>Motoyama, Keiichi</creator><creator>Arima, Hidetoshi</creator><creator>Mochinaga, Sakiko</creator><creator>Higaki, Katsumi</creator><creator>Ohno, Kousaku</creator><creator>Irie, Tetsumi</creator><general>The Pharmaceutical Society of Japan</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150601</creationdate><title>Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann–Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease</title><author>Tanaka, Yuta ; Yamada, Yusei ; Ishitsuka, Yoichi ; Matsuo, Muneaki ; Shiraishi, Koki ; Wada, Koki ; Uchio, Yushiro ; Kondo, Yuki ; Takeo, Toru ; Nakagata, Naomi ; Higashi, Taishi ; Motoyama, Keiichi ; Arima, Hidetoshi ; Mochinaga, Sakiko ; Higaki, Katsumi ; Ohno, Kousaku ; Irie, Tetsumi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-d4a188198ca002ca0db628f2557d29ae176660fb9dde4cf59acf0a6eb627ca903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>2-Hydroxypropyl-beta-cyclodextrin</topic><topic>2-hydroxypropyl-β-cyclodextrin</topic><topic>Animals</topic><topic>beta-Cyclodextrins - administration & dosage</topic><topic>beta-Cyclodextrins - blood</topic><topic>beta-Cyclodextrins - pharmacokinetics</topic><topic>beta-Cyclodextrins - therapeutic use</topic><topic>Cholesterol - metabolism</topic><topic>Disease Models, Animal</topic><topic>Humans</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver Diseases - etiology</topic><topic>Liver Diseases - metabolism</topic><topic>Liver Diseases - prevention & control</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Niemann-Pick Disease, Type C - complications</topic><topic>Niemann-Pick Disease, Type C - drug therapy</topic><topic>Niemann–Pick type C</topic><topic>Npc1-deficient mouse</topic><topic>Proteins - genetics</topic><topic>Solubility</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tanaka, Yuta</creatorcontrib><creatorcontrib>Yamada, Yusei</creatorcontrib><creatorcontrib>Ishitsuka, Yoichi</creatorcontrib><creatorcontrib>Matsuo, Muneaki</creatorcontrib><creatorcontrib>Shiraishi, Koki</creatorcontrib><creatorcontrib>Wada, Koki</creatorcontrib><creatorcontrib>Uchio, Yushiro</creatorcontrib><creatorcontrib>Kondo, Yuki</creatorcontrib><creatorcontrib>Takeo, Toru</creatorcontrib><creatorcontrib>Nakagata, Naomi</creatorcontrib><creatorcontrib>Higashi, Taishi</creatorcontrib><creatorcontrib>Motoyama, Keiichi</creatorcontrib><creatorcontrib>Arima, Hidetoshi</creatorcontrib><creatorcontrib>Mochinaga, Sakiko</creatorcontrib><creatorcontrib>Higaki, Katsumi</creatorcontrib><creatorcontrib>Ohno, Kousaku</creatorcontrib><creatorcontrib>Irie, Tetsumi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tanaka, Yuta</au><au>Yamada, Yusei</au><au>Ishitsuka, Yoichi</au><au>Matsuo, Muneaki</au><au>Shiraishi, Koki</au><au>Wada, Koki</au><au>Uchio, Yushiro</au><au>Kondo, Yuki</au><au>Takeo, Toru</au><au>Nakagata, Naomi</au><au>Higashi, Taishi</au><au>Motoyama, Keiichi</au><au>Arima, Hidetoshi</au><au>Mochinaga, Sakiko</au><au>Higaki, Katsumi</au><au>Ohno, Kousaku</au><au>Irie, Tetsumi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann–Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2015-06-01</date><risdate>2015</risdate><volume>38</volume><issue>6</issue><spage>844</spage><epage>851</epage><pages>844-851</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>Niemann–Pick type C disease (NPC), an autosomal recessive lysosomal storage disorder, is an inherited disease characterized by the accumulation of intracellular unesterified cholesterol. A solubilizing agent of lipophilic compounds, 2-hydroxypropyl-β-cyclodextrin (HPBCD), is an attractive drug candidate against NPC disease. However, establishment of the optimum dosage of HPBCD remains to be determined. In this study, we evaluated the effective dosage of HPBCD in NPC model (Npc1−/−) mice, and determined serum HPBCD concentrations. Subcutaneous injection of 1000–4000 mg/kg HPBCD improved the lifespan of Npc1−/− mice. In addition, liver injury and cholesterol sequestration were significantly prevented by 4000 mg/kg HPBCD in Npc1−/− mice. Serum HPBCD concentrations, when treated at the effective dosages (1000–4000 mg/kg), were approximately 1200–2500 µg/mL at 0.5 h after subcutaneous injection, and blood HPBCD concentrations were immediately eliminated in Npc1−/− mice. Furthermore, we examined serum HPBCD concentrations when treated at 40000 mg (approximately 2500 mg/kg) in a patient with NPC. We observed that the effective concentration in the in vivo study using Npc1−/− mice was similar to that in the patient. In the patient, systemic clearance and the volume of distribution of HPBCD were in accordance with the glomerular filtration rate and extracellular fluid volume, respectively. These results could provide useful information for developing the optimal dosage regimen for HPBCD therapy when administered intravenously to NPC patients.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>26027824</pmid><doi>10.1248/bpb.b14-00726</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0918-6158 |
ispartof | Biological and Pharmaceutical Bulletin, 2015/06/01, Vol.38(6), pp.844-851 |
issn | 0918-6158 1347-5215 |
language | eng |
recordid | cdi_proquest_miscellaneous_1685749257 |
source | Free Full-Text Journals in Chemistry |
subjects | 2-Hydroxypropyl-beta-cyclodextrin 2-hydroxypropyl-β-cyclodextrin Animals beta-Cyclodextrins - administration & dosage beta-Cyclodextrins - blood beta-Cyclodextrins - pharmacokinetics beta-Cyclodextrins - therapeutic use Cholesterol - metabolism Disease Models, Animal Humans Liver - drug effects Liver - metabolism Liver Diseases - etiology Liver Diseases - metabolism Liver Diseases - prevention & control Male Mice Mice, Knockout Niemann-Pick Disease, Type C - complications Niemann-Pick Disease, Type C - drug therapy Niemann–Pick type C Npc1-deficient mouse Proteins - genetics Solubility |
title | Efficacy of 2-Hydroxypropyl-β-cyclodextrin in Niemann–Pick Disease Type C Model Mice and Its Pharmacokinetic Analysis in a Patient with the Disease |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-23T20%3A43%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20of%202-Hydroxypropyl-%CE%B2-cyclodextrin%20in%20Niemann%E2%80%93Pick%20Disease%20Type%20C%20Model%20Mice%20and%20Its%20Pharmacokinetic%20Analysis%20in%20a%20Patient%20with%20the%20Disease&rft.jtitle=Biological%20&%20pharmaceutical%20bulletin&rft.au=Tanaka,%20Yuta&rft.date=2015-06-01&rft.volume=38&rft.issue=6&rft.spage=844&rft.epage=851&rft.pages=844-851&rft.issn=0918-6158&rft.eissn=1347-5215&rft_id=info:doi/10.1248/bpb.b14-00726&rft_dat=%3Cproquest_cross%3E1685749257%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c416t-d4a188198ca002ca0db628f2557d29ae176660fb9dde4cf59acf0a6eb627ca903%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1685749257&rft_id=info:pmid/26027824&rfr_iscdi=true |