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

The Prokinetic Cinitapride Has No Clinically Relevant Pharmacokinetic Interaction and Effect on QT during Coadministration with Ketoconazole

Marta Robert, Miquel Salvà, Rosa Segarra, Marco Pavesi, Ramón Esbri, David Roberts and Georg Golor
Drug Metabolism and Disposition July 2007, 35 (7) 1149-1156; DOI: https://doi.org/10.1124/dmd.106.010835
Marta Robert
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Miquel Salvà
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rosa Segarra
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marco Pavesi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ramón Esbri
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Roberts
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Georg Golor
  • 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 present clinical trial was designed to evaluate the possible pharmacokinetic and electrocardiographic interactions of the gastroenteric prokinetic drug cinitapride with ketoconazole. The safety and tolerability of the study treatments were also evaluated. After a placebo-controlled, double-blind, crossover design, 16 healthy male (n = 8) and female (n = 8) volunteers were randomized into four treatment groups of four subjects (two males and two females): cinitapride (CTP; 1 mg t.i.d.) + ketoconazole (KET; 200 mg b.i.d.), CTP + placebo (PL), PL+KET, and PL+PL. Treatments were given for 7 days with a washout period of 14 days between crossover treatments. Cinitapride is rapidly absorbed after oral administration and is metabolized by the cytochrome P450 CYP3A4 and CYP2C8 isozymes. At steady state, coadministration with ketoconazole, a potent CYP3A4 inhibitor, increased mean Cmax,ss and AUCτ by 1.63- and 1.98-fold, respectively. Measurement of mean QTc interval or baseline-corrected QTc intervals on day 7 showed small increases that were due to the effects of ketoconazole alone. Comparing CTP+KET versus PL+KET, the differences between mean increases in the QTc parameters were always less than 2 ms. Finally, no outlier increase of the QTc interval versus baseline >60 ms was identified after any treatment. The study showed that cinitapride, either given alone or after coadministration with ketoconazole 200 mg b.i.d., had no effect on cardiac repolarization as measured by changes in the heart rate-corrected QT interval on the surface electrocardiogram.

Footnotes

  • This study was funded by Laboratorios Almirall, S.A.

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

  • doi:10.1124/dmd.106.010835.

  • ABBREVIATIONS: MS/MS, tandem mass spectrometry; QT, duration in milliseconds from the beginning of Q wave to the end of the T wave; CTP, cinitapride; KET, ketoconazole; PL, placebo; AUCτ, area under the plasma concentration-time curve within a dosing interval; QTc, QT interval corrected for heart rate; ECG, electrocardiogram; FI, fluctuation index; RR, duration in milliseconds between two R peaks of two consecutive QRS complexes; PR, duration in milliseconds from the beginning of wave P to onset of ventricular depolarization (Q and R); QRS, duration in milliseconds of the QRS complex; QTcB, QT interval corrected by the Bazett formula (QT/RR1/2); QTcF, QT interval corrected by the Fridericia formula (QT/RR1/3); QTcL, QT linear correction model [QT + α × (1 – RR)]; QTcI, QT parabolic log/log correction model (QT/RRα); hERG, human ether-a-go-go-related gene; ANOVA, analysis of variance; CI, confidence interval; AE, adverse event.

    • Received April 27, 2006.
    • Accepted April 13, 2007.
  • 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: 35 (7)
Drug Metabolism and Disposition
Vol. 35, Issue 7
1 Jul 2007
  • 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.
The Prokinetic Cinitapride Has No Clinically Relevant Pharmacokinetic Interaction and Effect on QT during Coadministration with Ketoconazole
(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

The Prokinetic Cinitapride Has No Clinically Relevant Pharmacokinetic Interaction and Effect on QT during Coadministration with Ketoconazole

Marta Robert, Miquel Salvà, Rosa Segarra, Marco Pavesi, Ramón Esbri, David Roberts and Georg Golor
Drug Metabolism and Disposition July 1, 2007, 35 (7) 1149-1156; DOI: https://doi.org/10.1124/dmd.106.010835

Citation Manager Formats

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

Share
Research ArticleArticle

The Prokinetic Cinitapride Has No Clinically Relevant Pharmacokinetic Interaction and Effect on QT during Coadministration with Ketoconazole

Marta Robert, Miquel Salvà, Rosa Segarra, Marco Pavesi, Ramón Esbri, David Roberts and Georg Golor
Drug Metabolism and Disposition July 1, 2007, 35 (7) 1149-1156; DOI: https://doi.org/10.1124/dmd.106.010835
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

  • Series-Compartment Models of Hepatic Elimination
  • Warfarin PBPK Model with TMDD Mechanism
  • Identification of payload-containing catabolites of ADCs
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