Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Isosorbide dinitrate bioavailability, kinetics, and metabolism.

P Straehl, R L Galeazzi

    Clinical Pharmacology and Therapeutics
    |August 1, 1985
    PubMed
    Summary
    This summary is machine-generated.

    Related Concept Videos

    You might also read

    Related Articles

    Articles linked to this work by shared authors, journal, and citation graph.

    Sort by
    Same author

    From signal generation to proof of new drug event combinations in the comprehensive hospital drug monitoring, Berne/St. Gallen, 1974-1993; four examples.

    Pharmacoepidemiology and drug safety·2004
    Same author

    Cutaneous pseudolymphoma associated with bromocriptine therapy.

    Clinical endocrinology·2000
    Same author

    Epidemiology of drug exposure and adverse drug reactions in two swiss departments of internal medicine.

    British journal of clinical pharmacology·2000
    Same author

    [Unexpected development during rehabilitation for suspected rheumatic disorder].

    Praxis·1999
    Same author

    Medullary thyroid carcinoma in Graves' disease.

    Clinical endocrinology·1999
    Same author

    Relapsing Whipple's disease presenting with hypopituitarism.

    Clinical endocrinology·1999
    Same journal

    The Future of Clinical Pharmacology: The Right Medicine at the Right Dose for Each Patient.

    Clinical pharmacology and therapeutics·2026
    Same journal

    Effects of Trimethoprim on Three Previously Proposed Putative Biomarkers for OCT2/MATE-Mediated Renal Drug-Drug Interactions in Healthy Volunteers.

    Clinical pharmacology and therapeutics·2026
    Same journal

    Clinical Characterization of Enzyme and Transporter Precipitants to Evaluate Drug-Drug Interactions for Orforglipron, a Small Molecule Glucagon-Like Peptide-1 Receptor Agonist.

    Clinical pharmacology and therapeutics·2026
    Same journal

    Symposium Report: Stakeholders' Perspectives on Phase 1 Trials in Japanese Prior to Multi-Regional Clinical Trials and Future Pathways.

    Clinical pharmacology and therapeutics·2026
    Same journal

    Resolving CYP2D6 Structural Complexity with Long-Read Sequencing: Implications for Tamoxifen Precision Dosing in Thai Breast Cancer Patients.

    Clinical pharmacology and therapeutics·2026
    Same journal

    Identification of a Functional CYP2C8 Variant Allele that Alters Splicing, Reduces Protein Expression, and Increases Drug Exposure.

    Clinical pharmacology and therapeutics·2026
    See all related articles

    Isosorbide dinitrate (ISDN) bioavailability is similar for oral and sublingual routes, around 29%, due to significant first-pass metabolism. ISDN is rapidly metabolized into isosorbide 5-mononitrate and isosorbide 2-mononitrate, with 100% systemic availability of these metabolites.

    Area of Science:

    • Pharmacokinetics
    • Drug Metabolism
    • Cardiovascular Pharmacology

    Background:

    • Isosorbide dinitrate (ISDN) is a vasodilator used for angina.
    • Understanding ISDN's absorption, distribution, metabolism, and excretion (ADME) is crucial for optimizing its therapeutic use.
    • Previous studies have investigated ISDN pharmacokinetics, but detailed comparisons of different routes and metabolite kinetics are needed.

    Purpose of the Study:

    • To investigate the pharmacokinetics of isosorbide dinitrate (ISDN) following intravenous administration.
    • To determine the bioavailability of sublingual and oral ISDN preparations.
    • To characterize the plasma levels and disposition of ISDN metabolites, isosorbide 5-mononitrate (IS-5-MN) and isosorbide 2-mononitrate (IS-2-MN).

    Main Methods:

    Related Experiment Videos

  • Plasma concentrations of ISDN, IS-5-MN, and IS-2-MN were quantified using gas-liquid chromatography (GLC).
  • Pharmacokinetic parameters were determined using biexponential and two-compartment body models for ISDN and mononitrates, respectively.
  • Bioavailability and systemic availability were calculated for oral, sublingual, and intravenous routes.

    • Main Results:

    • ISDN exhibited rapid distribution (t1/2 of 4.7 min IV, 8.7 min SL) and a terminal half-life of approximately 50 minutes across routes.
    • Oral and sublingual ISDN bioavailability was similar (~29%), indicating significant hepatic first-pass metabolism.
    • Mononitrate metabolites (IS-5-MN and IS-2-MN) showed 100% systemic availability after oral/sublingual ISDN, with terminal half-lives of 4.33 hours and 1.83 hours, respectively.

    Conclusions:

    • Sublingual ISDN dosing does not circumvent the first-pass effect, resulting in comparable bioavailability to oral administration.
    • Extrahepatic metabolism contributes to the rapid clearance of ISDN, exceeding normal hepatic blood flow.
    • ISDN is extensively converted to its mononitrate metabolites, with IS-5-MN being the predominant form (75% vs. 25% for IS-2-MN).