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

Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats

Sarah White, Elizabeth Laurenzana, Howard Hendrickson, W. Brooks Gentry and S. Michael Owens
Drug Metabolism and Disposition September 2011, 39 (9) 1718-1726; DOI: https://doi.org/10.1124/dmd.111.039446
Sarah White
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elizabeth Laurenzana
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Howard Hendrickson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
W. Brooks Gentry
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Michael Owens
  • 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

We tested the hypothesis that differences in (+)-methamphetamine (METH) disposition during late rat pregnancy could lead to increased vulnerability to acute METH effects. The disposition of a single 1 mg/kg i.v. METH dose was studied during early (gestation day 7, GD7) and late (GD21) gestation. Results showed gestation time-dependent pharmacokinetics, characterized by a significantly higher area under the METH serum concentration versus time curve and a lower clearance on GD21 (p < 0.05; total, renal, and nonrenal clearance). The terminal elimination half-life (t1/2λz) of METH and (+)-amphetamine (AMP; a pharmacologically active metabolite of METH) were not different on GD7, but by GD21, AMP t1/2λz was 37% longer than METH t1/2λz (p < 0.05). To identify the mechanism for AMP metabolite changes, intravenous AMP pharmacokinetics on GD21 were compared with AMP metabolite pharmacokinetics after intravenous METH. The intravenous AMP t1/2λz was significantly shorter than metabolite AMP t1/2λz (p < 0.05), which suggested AMP metabolite formation (not elimination) was the rate-limiting process. To understand the medical consequence of METH use during late-stage pregnancy, timed-pregnant rats received an intravenous dose of saline or METH (1, 3, or 5.6 mg/kg) on GD21, 0 to 2 days antepartum. Although one rat died and another had stillbirths at term after the 5.6-mg/kg dose, the pharmacokinetic values for all of the other animals were not significantly different. In conclusion, late-gestational clearance reductions lengthen METH exposure time, possibly increasing susceptibility to adverse effects, including death.

Footnotes

  • This work was supported by the National Institutes of Health National Institute on Drug Abuse [Grant DA07610]; the National Institutes of Health National Institute of Environmental Health Sciences [Grant T32-EA07310]; the National Institutes of Health National Center for Research Resources [Grant UL1-RR029884]; and a graduate fellowship from GlaxoSmithKline.

  • S.M.O. and W.B.G. have financial interests in and serve as Chief Scientific Officer and Chief Medical Officer, respectively, of InterveXion Therapeutics LLC (Little Rock, AR), a pharmaceutical biotechnology company focused on treating human drug addiction with antibody-based therapy.

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

    doi:10.1124/dmd.111.039446.

  • ABBREVIATIONS:

    METH
    (+)-methamphetamine
    ANOVA
    analysis of variance
    AMP
    (+)-amphetamine
    AUC0∞
    area under the serum concentration-versus-time curve from time zero to infinity
    ClNR
    nonrenal clearance
    ClR
    renal clearance
    ClT
    total body clearance
    Cl/F
    systemic clearance corrected for bioavailability
    GD
    gestation day
    fm
    fraction of parent drug converted to a metabolite
    fu
    fraction of unchanged parent drug in urine
    GD
    gestational day
    λz
    terminal elimination rate constant
    LC
    liquid chromatography
    LLE
    liquid-liquid phase extraction
    MRT
    mean residence time
    PND
    postnatal day
    t1/2λz
    terminal elimination half-life
    Vd
    volume of distribution
    Vdss
    volume of distribution at steady state.

  • Received March 18, 2011.
  • Accepted June 1, 2011.
  • Copyright © 2011 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: 39 (9)
Drug Metabolism and Disposition
Vol. 39, Issue 9
1 Sep 2011
  • 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.
Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats
(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

Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats

Sarah White, Elizabeth Laurenzana, Howard Hendrickson, W. Brooks Gentry and S. Michael Owens
Drug Metabolism and Disposition September 1, 2011, 39 (9) 1718-1726; DOI: https://doi.org/10.1124/dmd.111.039446

Citation Manager Formats

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

Share
Research ArticleArticle

Gestation Time-Dependent Pharmacokinetics of Intravenous (+)-Methamphetamine in Rats

Sarah White, Elizabeth Laurenzana, Howard Hendrickson, W. Brooks Gentry and S. Michael Owens
Drug Metabolism and Disposition September 1, 2011, 39 (9) 1718-1726; DOI: https://doi.org/10.1124/dmd.111.039446
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
    • Results
    • Discussion
    • Authorship Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Improved CYP Reaction Phenotyping
  • Multiple-Concentration Chemical Inhibition Design
  • New Dog P450 3A98 in Gut
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