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

Population one-compartment pharmacokinetic analysis with missing dosage data.

Dolors Soy1, Stuart L Beal, Lewis B Sheiner

  • 1Department of Biopharmaceutical Sciences, School of Pharmacy, University of California San Francisco, 94143-0626, USA.

Clinical Pharmacology and Therapeutics
|November 13, 2004
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

Effects of malaria intermittent preventive treatment with dihydroartemisinin-piperaquine on antiretroviral drug concentrations in African pregnant women living with HIV.

Antimicrobial agents and chemotherapy·2026
Same author

[Translated article] Assessment of serum creatinine-based equations for estimating glomerular filtration rate in critically ill patients with or without augmented renal clearance.

Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria·2026
Same author

Half-dose glucarpidase: an effective rescue for toxic methotrexate plasma concentrations in a patient with bilateral primary vitreoretinal lymphoma.

Annals of hematology·2026
Same author

Assessment of serum creatinine-based equations for estimating glomerular filtration rate in critically ill patients with or without augmented renal clearance.

Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria·2026
Same author

Obinutuzumab for B-cell depletion prior to kidney transplant in a highly sensitized patient with anaphylactic reaction to rituximab.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists·2025
Same author

Compatibility and Physico-Chemical Stability of Six Intravenous Mixtures for Postoperative Multimodal Analgesia.

Drug design, development and therapy·2025
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

Robust pharmacokinetic analysis methods accurately assess drug dosage history, even with missing information. These methods are reliable for outpatient drug therapy, unlike those assuming correct nominal dosing.

Area of Science:

  • Pharmacokinetics
  • Drug Development
  • Clinical Pharmacology

Background:

  • Accurate pharmacokinetic (PK) analysis is crucial for effective drug therapy.
  • Missing or incorrect prior dosage history poses a significant challenge in population PK modeling.
  • Existing methods may not be robust to deviations in patient-reported or prescribed drug intake.

Purpose of the Study:

  • To develop and evaluate population 1-compartment PK analysis methods for scenarios with suspect or missing prior dosage history.
  • To compare the precision and bias of different PK analysis methods under varying drug accumulation conditions.

Main Methods:

  • Simulated population PK data from a 1-compartment model with first-order elimination and absorption.
  • Evaluated methods included Missing Dose Method (MDM), Missing Dose Mixture Method (MDMM), Extrapolation-Subtraction Method (ESM), Prescribed Dose Method (PDM), and an Ideal Method (IDM).

Related Experiment Videos

  • Compared method performance under conditions of high drug accumulation (t1/2 ≈ τ) and low accumulation (t1/2 ≈ τ/5).

    • Main Results:

    • When drug accumulation is considerable (t1/2 ≈ τ), MDM and MDMM demonstrated the highest precision.
    • The Prescribed Dose Method (PDM) and Extrapolation-Subtraction Method (ESM) showed poor accuracy in this scenario.
    • No significant differences in precision or bias were observed between methods when drug accumulation was low (t1/2 ≈ τ/5).
    • Analysis of real caffeine data corroborated simulation findings.

    Conclusions:

    • Population PK analysis methods that do not rely on assumed nominal dosage history are robust and reliable.
    • Methods assuming correct nominal dose history are not robust to misspecification of past dosage.
    • These findings are particularly relevant for intensive PK studies during outpatient drug therapy.