Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Alpha-Amylase Inhibitor, CS-1036 Binds to Serum Amylase in a Concentration-Dependent and Saturable Manner

Tomohiro Honda, Yoko Kaneno-Urasaki, Takashi Ito, Takako Kimura, Nobuko Matsushima, Hiromi Okabe, Atsushi Yamasaki and Takashi Izumi
Drug Metabolism and Disposition March 2014, 42 (3) 326-333; DOI: https://doi.org/10.1124/dmd.113.054452
Tomohiro Honda
Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.H., Y.K.-U., T.It., T.Iz.); Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.K.); Translational Medicine & Clinical Pharmacology Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (N.M., H.O.); and Global Project Management Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (A.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoko Kaneno-Urasaki
Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.H., Y.K.-U., T.It., T.Iz.); Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.K.); Translational Medicine & Clinical Pharmacology Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (N.M., H.O.); and Global Project Management Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (A.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takashi Ito
Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.H., Y.K.-U., T.It., T.Iz.); Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.K.); Translational Medicine & Clinical Pharmacology Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (N.M., H.O.); and Global Project Management Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (A.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takako Kimura
Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.H., Y.K.-U., T.It., T.Iz.); Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.K.); Translational Medicine & Clinical Pharmacology Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (N.M., H.O.); and Global Project Management Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (A.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nobuko Matsushima
Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.H., Y.K.-U., T.It., T.Iz.); Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.K.); Translational Medicine & Clinical Pharmacology Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (N.M., H.O.); and Global Project Management Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (A.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiromi Okabe
Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.H., Y.K.-U., T.It., T.Iz.); Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.K.); Translational Medicine & Clinical Pharmacology Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (N.M., H.O.); and Global Project Management Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (A.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Atsushi Yamasaki
Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.H., Y.K.-U., T.It., T.Iz.); Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.K.); Translational Medicine & Clinical Pharmacology Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (N.M., H.O.); and Global Project Management Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (A.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takashi Izumi
Drug Metabolism & Pharmacokinetics Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.H., Y.K.-U., T.It., T.Iz.); Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (T.K.); Translational Medicine & Clinical Pharmacology Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (N.M., H.O.); and Global Project Management Department, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo, Japan (A.Y.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

(2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-β-D-glucopyranosyl)-α-D-glucopyranoside (CS-1036), which is an α-amylase inhibitor, exhibited biphasic and sustained elimination with a long t1/2 (18.4–30.0 hours) in rats and monkeys, but exhibited a short t1/2 (3.7–7.9 hours) in humans. To clarify the species differences in the t1/2, the plasma protein binding of CS-1036 was evaluated by ultrafiltration. A concentration-dependent and saturable plasma protein binding of CS-1036 was observed in rats and monkeys with the dissociation rate constant (KD) of 8.95 and 27.2 nM, and maximal binding capacity (Bmax) of 52.8 and 22.1 nM, respectively. By the assessments of the recombinant amylase and immunoprecipitation, the major binding protein of CS-1036 in rats was identified as salivary amylase (KD 5.64 nM). CS-1036 also showed concentration-dependent and saturable binding to human salivary and pancreatic amylase, with similar binding affinity in rats. However, the protein binding of CS-1036 was constant in human plasma (≤10.2%) due to the lower serum amylase level compared with rats and monkeys. From the calculation of the unbound fraction (fu) in plasma based on in vitro KD and Bmax, the dose-dependent increase in fu after oral administration is speculated to lead to a dose-dependent increase in total body clearance and a high area under the curve/dose at lower doses, such as 0.3 mg/kg in rats.

Footnotes

    • Received August 23, 2013.
    • Accepted December 6, 2013.
  • dx.doi.org/10.1124/dmd.113.054452.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 42 (3)
Drug Metabolism and Disposition
Vol. 42, Issue 3
1 Mar 2014
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Alpha-Amylase Inhibitor, CS-1036 Binds to Serum Amylase in a Concentration-Dependent and Saturable Manner
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

CS-1036 Binds to Serum Amylase

Tomohiro Honda, Yoko Kaneno-Urasaki, Takashi Ito, Takako Kimura, Nobuko Matsushima, Hiromi Okabe, Atsushi Yamasaki and Takashi Izumi
Drug Metabolism and Disposition March 1, 2014, 42 (3) 326-333; DOI: https://doi.org/10.1124/dmd.113.054452

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

CS-1036 Binds to Serum Amylase

Tomohiro Honda, Yoko Kaneno-Urasaki, Takashi Ito, Takako Kimura, Nobuko Matsushima, Hiromi Okabe, Atsushi Yamasaki and Takashi Izumi
Drug Metabolism and Disposition March 1, 2014, 42 (3) 326-333; DOI: https://doi.org/10.1124/dmd.113.054452
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Warfarin PBPK Model with TMDD Mechanism
  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics