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

Pharmacokinetic Study of Enclosed Hemoglobin and Outer Lipid Component after the Administration of Hemoglobin Vesicles as an Artificial Oxygen Carrier

Kazuaki Taguchi, Yukino Urata, Makoto Anraku, Toru Maruyama, Hiroshi Watanabe, Hiromi Sakai, Hirohisa Horinouchi, Koichi Kobayashi, Eishun Tsuchida, Toshiya Kai and Masaki Otagiri
Drug Metabolism and Disposition July 2009, 37 (7) 1456-1463; DOI: https://doi.org/10.1124/dmd.109.027094
Kazuaki Taguchi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yukino Urata
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Makoto Anraku
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toru Maruyama
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Watanabe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiromi Sakai
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hirohisa Horinouchi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Koichi Kobayashi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eishun Tsuchida
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toshiya Kai
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masaki Otagiri
  • 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

The hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates a concentrated Hb solution in lipid vesicles (liposomes). The pharmacokinetic properties of HbV were investigated in mice and rats. With use of HbV in which the internal Hb was labeled with 125I (125I-HbV) and cell-free 125I-Hb, it was found that encapsulation of Hb increased the half-life by 30 times, accompanied by decreased distribution in both the liver and kidney. The half-life of HbV was increased, and the uptake clearance for the liver and spleen were decreased with increasing doses of HbV. In an in vitro study, the specific uptake and degradation of HbV in RAW 264.7 cells were found, but this was not the case for parenchymal and endothelial cells. The pharmacokinetics of HbV components (internal Hb and liposomal lipid) were also investigated using 125I-HbV and 3H-HbV (liposomal cholesterol was radiolabeled with tritium-3). The time courses for the plasma concentration curves of 125I-HbV, 3H-HbV, and iron derived from HbV suggest that HbV maintain an intact structure in the blood circulation up to 24 h after injection. 125I-HbV and 3H-HbV were distributed mainly to the liver and spleen. Internal Hb disappeared from both the liver and spleen 5 days after injection, and the liposomal cholesterol disappeared at approximately 14 days. Internal Hb was excreted into the urine and cholesterol into feces via biliary excretion. These results suggest that the HbV has a reasonable blood retention and metabolic and excretion performance and could be used as an oxygen carrier.

Footnotes

  • This work was supported in part by the Ministry of Health, Labour and Welfare, Japan [Health Science Research Grants (Health Science Research Including Drug Innovation)].

  • K.T. and Y.U. contributed equally to this work.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.109.027094.

  • ABBREVIATIONS: RBC, red blood cell; HbV, hemoglobin vesicle(s); PEG, polyethylene glycol; NO, nitric oxide; 125I-HbV, 125I-labeled hemoglobin vesicle; 3H-HbV, 3H-labeled hemoglobin vesicle; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine; rHSA, recombinant human serum albumin; BSA, bovine serum albumin; TCA, trichloroacetic acid; PBS, phosphate-buffered saline; WE, Williams' E medium; FCS, fetal calf serum; AUC, area under the concentration-time curve; MPS, mononuclear phagocyte system; ID, injected dose; Hp, haptoglobin; CLuptake, uptake clearance.

    • Accepted April 9, 2009.
    • Received February 11, 2009.
  • 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: 37 (7)
Drug Metabolism and Disposition
Vol. 37, Issue 7
1 Jul 2009
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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.
Pharmacokinetic Study of Enclosed Hemoglobin and Outer Lipid Component after the Administration of Hemoglobin Vesicles as an Artificial Oxygen Carrier
(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

Pharmacokinetic Study of Enclosed Hemoglobin and Outer Lipid Component after the Administration of Hemoglobin Vesicles as an Artificial Oxygen Carrier

Kazuaki Taguchi, Yukino Urata, Makoto Anraku, Toru Maruyama, Hiroshi Watanabe, Hiromi Sakai, Hirohisa Horinouchi, Koichi Kobayashi, Eishun Tsuchida, Toshiya Kai and Masaki Otagiri
Drug Metabolism and Disposition July 1, 2009, 37 (7) 1456-1463; DOI: https://doi.org/10.1124/dmd.109.027094

Citation Manager Formats

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

Share
Research ArticleArticle

Pharmacokinetic Study of Enclosed Hemoglobin and Outer Lipid Component after the Administration of Hemoglobin Vesicles as an Artificial Oxygen Carrier

Kazuaki Taguchi, Yukino Urata, Makoto Anraku, Toru Maruyama, Hiroshi Watanabe, Hiromi Sakai, Hirohisa Horinouchi, Koichi Kobayashi, Eishun Tsuchida, Toshiya Kai and Masaki Otagiri
Drug Metabolism and Disposition July 1, 2009, 37 (7) 1456-1463; DOI: https://doi.org/10.1124/dmd.109.027094
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
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Determination of Acyl-, O-, and N-Glucuronide
  • TMDD Affects PK of IL-10 Fc-fusion Proteins
  • Uptake as the RDS in Pevonedistat Hepatic Clearance
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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics