Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

A Comparison of Pharmacokinetics between Humans and Monkeys

Takafumi Akabane, Kenji Tabata, Keitaro Kadono, Shuichi Sakuda, Shigeyuki Terashita and Toshio Teramura
Drug Metabolism and Disposition February 2010, 38 (2) 308-316; DOI: https://doi.org/10.1124/dmd.109.028829
Takafumi Akabane
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenji Tabata
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keitaro Kadono
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shuichi Sakuda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shigeyuki Terashita
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toshio Teramura
  • 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

To verify the availability of pharmacokinetic parameters in cynomolgus monkeys, hepatic availability (Fh) and the fraction absorbed multiplied by intestinal availability (FaFg) were evaluated to determine their contributions to absolute bioavailability (F) after intravenous and oral administrations. These results were compared with those for humans using 13 commercial drugs for which human pharmacokinetic parameters have been reported. In addition, in vitro studies of these drugs, including membrane permeability, intrinsic clearance, and p-glycoprotein affinity, were performed to classify the drugs on the basis of their pharmacokinetic properties. In the present study, monkeys had a markedly lower F than humans for 8 of 13 drugs. Although there were no obvious differences in Fh between humans and monkeys, a remarkable species difference in FaFg was observed. Subsequently, we compared the FaFg values for monkeys with the in vitro pharmacokinetic properties of each drug. No obvious FaFg differences were observed between humans and monkeys for drugs that undergo almost no in vivo metabolism. In contrast, low FaFg were observed in monkeys for drugs that undergo relatively high metabolism in monkeys. These results suggest that first-pass intestinal metabolism is greater in cynomolgus monkeys than in humans, and that bioavailability in cynomolgus monkeys after oral administration is unsuitable for predicting pharmacokinetics in humans. In addition, a rough correlation was also observed between in vitro metabolic stability and Fg in humans, possibly indicating the potential for Fg prediction in humans using only in vitro parameters after slight modification of the evaluation system for in vitro intestinal metabolism.

Footnotes

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

    doi:10.1124/dmd.109.028829.

  • Fa
    fraction absorbed
    Fg
    intestinal availability
    Fh
    hepatic availability
    F
    bioavailability
    MDZ
    midazolam
    P450
    cytochrome P450
    P-gp
    p-glycoprotein
    Rb
    blood-to-plasma concentration ratio
    CLint
    intrinsic clearance
    CLintliver
    CLint in liver microsomes
    CLintintestine
    CLint in intestine microsomes
    TAC
    tacrolimus
    Li
    lithium carbonate
    HT
    hydrochlorothiazide
    VER
    verapamil
    PRO
    propranolol
    AMI
    amitriptyline
    DEX
    dexamethasone
    NIF
    nifedipine
    QID
    quinidine
    TIM
    timolol
    IBU
    ibuprofen
    DIG
    digoxin
    LC
    liquid chromatography
    MS/MS
    mass spectrometry
    HPLC
    high-performance liquid chromatography
    PAMPA
    parallel artificial membrane permeability assay
    fp
    unbound drug fraction in plasma
    fb
    unbound drug fraction in blood
    ke
    disappearance rate constant
    AUC
    area under the plasma concentration-time curve
    fe
    urinary excretion ratio of unchanged
    CLh
    hepatic clearance
    CLt
    total clearance
    Qh
    blood flow rate in the liver
    SF
    scaling factor
    Papp
    apparent permeability.

    • Received June 5, 2009.
    • Accepted November 11, 2009.
  • Copyright © 2010 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: 38 (2)
Drug Metabolism and Disposition
Vol. 38, Issue 2
1 Feb 2010
  • 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.
A Comparison of Pharmacokinetics between Humans and Monkeys
(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

A Comparison of Pharmacokinetics between Humans and Monkeys

Takafumi Akabane, Kenji Tabata, Keitaro Kadono, Shuichi Sakuda, Shigeyuki Terashita and Toshio Teramura
Drug Metabolism and Disposition February 1, 2010, 38 (2) 308-316; DOI: https://doi.org/10.1124/dmd.109.028829

Citation Manager Formats

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

A Comparison of Pharmacokinetics between Humans and Monkeys

Takafumi Akabane, Kenji Tabata, Keitaro Kadono, Shuichi Sakuda, Shigeyuki Terashita and Toshio Teramura
Drug Metabolism and Disposition February 1, 2010, 38 (2) 308-316; DOI: https://doi.org/10.1124/dmd.109.028829
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike 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

  • In Vivo Functional Effects of CYP2C9 M1L
  • Clearance pathways: fevipiprant with probenecid perpetrator
  • Predicting Volume of Distribution from In Vitro Parameters
Show more Articles

Similar Articles

  • 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics