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

Simultaneous vs. sequential analysis for population PK/PD data II: robustness of methods.

Liping Zhang1, Stuart L Beal, Lewis B Sheinerz

  • 1Program in Biological and Medical Informatics, UCSF, USA.

Journal of Pharmacokinetics and Pharmacodynamics
|March 6, 2004
PubMed
Summary

When fitting pharmacokinetic/pharmacodynamic (PK/PD) models, misspecification impacts methods differently. A sequential approach using a non-parametric PK model offers superior performance in severe PK model misspecification scenarios.

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

Spatiotemporal sharply autofocused dual-Airy-ring Airy Gaussian vortex wave packets.

Optics letters·2018
Same author

Correlation of Gli1 and HER2 expression in gastric cancer: Identification of novel target.

Scientific reports·2018
Same author

Hypertension Control in Adults With CKD in China: Baseline Results From the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE).

American journal of hypertension·2018
Same author

Necrostatin-1 Protects Against Paraquat-Induced Cardiac Contractile Dysfunction via RIP1-RIP3-MLKL-Dependent Necroptosis Pathway.

Cardiovascular toxicology·2018
Same author

ФC31 Integrase-Mediated Isolation and Characterization of Novel Safe Harbors for Transgene Expression in the Pig Genome.

International journal of molecular sciences·2018
Same author

Proteomic analyses of ram (Ovis aries) testis during different developmental stages.

Animal reproduction science·2017

Area of Science:

  • Pharmacokinetics and Pharmacodynamics
  • Mathematical Modeling
  • Statistical Analysis

Background:

  • Joint modeling of pharmacokinetic (PK) and pharmacodynamic (PD) data is crucial for understanding drug behavior.
  • Previous work indicated sequential PK/PD modeling is computationally efficient when models align.
  • This study investigates model misspecification impacts on PK/PD analysis.

Purpose of the Study:

  • Compare simultaneous and sequential PK/PD modeling methods under model misspecification.
  • Evaluate predictive performance and Type I error rates.
  • Assess sensitivity to misspecification using real-world data.

Main Methods:

  • Simulated PK/PD data using NONMEM with one- or two-compartment PK and Emax PD models.
  • Fit data using simultaneous and sequential methods with misspecified models.

Related Experiment Videos

  • Analyzed real PK/PD data from vecuronium administration.

    • Main Results:

    • Simultaneous PK/PD modeling showed higher precision when only the PK model was misspecified.
    • A sequential method with a non-parametric PK model excelled in severe PK misspecification.
    • PD model misspecification affected simultaneous and sequential methods similarly.
    • Real data analysis revealed PK model sensitivity to PD misspecification.

    Conclusions:

    • The choice of PK/PD modeling strategy is critical when data-analytic models are misspecified.
    • Non-parametric sequential PK modeling is robust to severe PK misspecification.
    • Simultaneous PK/PD fitting can be sensitive to PD model misspecification, offering a diagnostic potential.