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

A note on confidence intervals with extended least squares parameter estimates.

L B Sheiner, S L Beal

    Journal of Pharmacokinetics and Biopharmaceutics
    |February 1, 1987
    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

    Pharmacodynamic measurements of methyl nicotinate percutaneous absorption.

    Pharmaceutical research·2013
    Same author

    A new Bayesian method to forecast and fine tune individual hemodialysis dose.

    Hemodialysis international. International Symposium on Home Hemodialysis·2009
    Same author

    Ways to fit a PK model with some data below the quantification limit.

    Journal of pharmacokinetics and pharmacodynamics·2002
    Same author

    Selecting reliable pharmacokinetic data for explanatory analyses of clinical trials in the presence of possible noncompliance.

    Journal of pharmacokinetics and pharmacodynamics·2001
    Same author

    The need for mixed-effects modeling with population dichotomous data.

    Journal of pharmacokinetics and pharmacodynamics·2001
    Same author

    Evaluating pharmacokinetic/pharmacodynamic models using the posterior predictive check.

    Journal of pharmacokinetics and pharmacodynamics·2001
    Same journal

    Integrated equation to evaluate accumulation profiles of drugs eliminated by Michaelis-Menten kinetics.

    Journal of pharmacokinetics and biopharmaceutics·2010
    Same journal

    Applications of a recirculatory stochastic pharmacokinetic model: limitations of compartmental models.

    Journal of pharmacokinetics and biopharmaceutics·2010
    Same journal

    Effect of plasma protein and tissue binding on the time course of drug concentration in plasma.

    Journal of pharmacokinetics and biopharmaceutics·2010
    Same journal

    Pharmacokinetics of methotrexate in solid tumors.

    Journal of pharmacokinetics and biopharmaceutics·2010
    Same journal

    Single- and multiple-dose kinetics of oral lorazepam in humans: the predictability of accumulation.

    Journal of pharmacokinetics and biopharmaceutics·2010
    Same journal

    Comparison of the in vitro and in vivo release of digoxin from four different soft gelatin capsule formulations.

    Journal of pharmacokinetics and biopharmaceutics·2010
    See all related articles

    The extended least squares (ELS) method for pharmacokinetic modeling shows poor performance with confidence intervals. Adjustments to ELS confidence intervals improve accuracy for pharmacokinetic parameter estimation.

    Area of Science:

    • Pharmacokinetics
    • Statistical Modeling
    • Biostatistics

    Background:

    • Extended Least Squares (ELS) is preferred for pharmacokinetic models with heteroscedasticity.
    • Standard ELS confidence intervals may not achieve the nominal 95% coverage level.
    • Ordinary Least Squares (OLS) intervals sometimes outperform ELS intervals.

    Purpose of the Study:

    • To evaluate the performance of ELS confidence intervals for pharmacokinetic parameters.
    • To identify and test adjustments to improve ELS interval accuracy.
    • To provide recommendations for kineticists using the ELS method.

    Main Methods:

    • Simulations were conducted using various pharmacokinetic and error variance models.
    • Confidence intervals were computed using ELS and OLS methods.

    Related Experiment Videos

  • Two adjustments were applied to ELS confidence intervals: bias correction and a 99% target level.

    • Main Results:

    • ELS confidence intervals at 95% target level showed significantly less than 95% coverage.
    • OLS intervals demonstrated better performance than standard ELS intervals.
    • The combined adjustments (bias correction and 99% target level) improved ELS interval coverage.

    Conclusions:

    • Standard ELS confidence intervals may be unreliable for pharmacokinetic parameter estimation.
    • Adjustments to ELS confidence intervals are necessary for accurate coverage.
    • Kineticists should consider applying bias correction and using a 99% target level for ELS intervals.