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 Concept Videos

Determination of Multiple Dosing Parameters: Loading and Maintenance Doses01:25

Determination of Multiple Dosing Parameters: Loading and Maintenance Doses

346
A loading dose is an essential pharmacological strategy to rapidly achieve the target plasma drug concentration necessary for an immediate therapeutic effect. This approach is especially critical for drugs characterized by slow absorption or extended half-lives, where delaying therapeutic plasma levels could compromise treatment outcomes. By administering a loading dose, clinicians ensure a prompt onset of drug action, even for agents with complex pharmacokinetic profiles.Achieving steady-state...
346
Dose Size and Dosing Frequency: Determination Methods01:21

Dose Size and Dosing Frequency: Determination Methods

498
Determining the optimal dose size and dosing frequency in pharmacotherapy is crucial for achieving therapeutic effectiveness while minimizing adverse effects. This article explores the methodologies employed in determining these parameters, focusing on their significance and interplay to tailor dosing regimens.Dose Size: Dose size refers to the amount of a drug administered in a single dose. It is determined based on the drug's pharmacodynamics and pharmacokinetics properties and...
498
Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant01:25

Drug Dosing in Renal Diseases: Dose Adjustments Based on Drug Clearance and Elimination Rate Constant

301
In patients with renal disease, dosage adjustments are necessary to maintain therapeutic plasma drug concentrations and prevent toxicity or subtherapeutic exposure. Renal impairment alters drug pharmacokinetics, especially in conditions like uremia, where changes such as prolonged elimination half-life and altered apparent volume of distribution can significantly affect drug disposition. These changes require careful modification of the dosing regimen to achieve the desired clinical...
301
Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

254
It is not uncommon for complete drug pharmacokinetic profiles to remain elusive in pharmacokinetics. This necessitates certain educated assumptions by pharmacokineticists to determine appropriate dosage regimens without comprehensive pharmacokinetic data from animal or human studies. One prevalent assumption is setting the bioavailability factor, denoted as F, to 1 or 100%. This assumption caters to the scenario where a drug doesn't achieve full systemic absorption, resulting in the patient...
254
Dosage Regimens: Designs and Approaches01:28

Dosage Regimens: Designs and Approaches

456
Designing a dosage regimen, which refers to the manner of drug administration, is a complex process involving the selection of drug dose, route, and frequency. This process is underpinned by pharmacokinetic parameters derived from tests and population averages. These parameters are then tailored to patient-specific variables such as diagnosis, demographics, and allergy status. Once therapy commences, therapeutic response monitoring is critical and achieved through clinical and physical...
456
Drug Dosing: Geriatric Patients01:15

Drug Dosing: Geriatric Patients

345
Elderly individuals encompass a diverse population with varying degrees of age-related physiological changes. Defining the elderly presents challenges, as the geriatric population is often arbitrarily categorized as individuals older than 65. However, many individuals in this group lead active and healthy lives, with an increasing number surpassing 85 years and falling into the older elderly category. Physiological changes associated with aging impact performance capacity and homeostatic...
345

You might also read

Related Articles

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

Sort by
Same author

Practical considerations when using the covariate-adjusted log-rank test for the analysis of time-to-event endpoints in oncology trials.

Biometrics·2026
Same author

Adaptive Designs in Trials With Time-to-Event Endpoints and Covariate Adjustment.

Statistics in medicine·2026
Same author

All Lines Is the Right Approach: Selecting Patient Lines of Therapy for an External Comparator Arm.

Pharmacoepidemiology and drug safety·2025
Same author

SHaploseek is a sequencing-only, high-resolution method for comprehensive preimplantation genetic testing.

Scientific reports·2023
Same author

Considerations for pooling real-world data as a comparator cohort to a single arm trial: a simulation study on assessment of heterogeneity.

BMC medical research methodology·2023
Same author

Implementation of Systematic Financial Screening in an Outpatient Breast Oncology Setting.

JCO clinical cancer informatics·2023

Related Experiment Video

Updated: Mar 24, 2026

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
09:44

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction

Published on: January 29, 2019

10.7K

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

Shing M Lee1, Daniel Backenroth2, Ying Kuen Ken Cheung2

  • 1Shing M. Lee, Daniel Backenroth, Ying Kuen Ken Cheung, and Dawn L. Hershman, Columbia University, New York, NY; Diana Vulih and Barry Anderson, Theradex Systems, Princeton, NJ; and Percy Ivy and Lori Minasian, National Cancer Institute, Bethesda, MD. sml2114@columbia.edu.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|March 2, 2016
PubMed
Summary
This summary is machine-generated.

The approved dose of bortezomib may exceed safe limits, with over 50% experiencing dose-limiting toxicities. Future studies should consider late-onset toxicities for molecularly targeted agents (MTAs) to find optimal doses.

More Related Videos

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
09:41

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

9.2K
Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
15:04

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation

Published on: January 19, 2019

12.9K

Related Experiment Videos

Last Updated: Mar 24, 2026

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction
09:44

Pretargeted Radioimmunotherapy Based on the Inverse Electron Demand Diels-Alder Reaction

Published on: January 29, 2019

10.7K
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
09:41

An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

9.2K
Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
15:04

Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation

Published on: January 19, 2019

12.9K

Area of Science:

  • Oncology
  • Clinical Pharmacology

Background:

  • Current dose-finding methods for anticancer agents are based on cytotoxic chemotherapy paradigms.
  • Molecularly targeted agents (MTAs) exhibit distinct toxicity profiles, including late-onset and cumulative toxicities, often leading to poor tolerability and post-marketing dose adjustments.
  • Bortezomib, a proteasome inhibitor, has shown tolerability issues necessitating dose re-evaluation.

Purpose of the Study:

  • To analyze the toxicity profile of bortezomib using data from completed dose-finding trials.
  • To optimize the dosing of bortezomib based on observed toxicities.
  • To evaluate the suitability of current dose-finding study designs for identifying optimal doses of MTAs.

Main Methods:

  • Retrospective analysis of toxicity data from 481 patients across 14 bortezomib dose-finding studies.
  • Classification of toxicities and computation of the incidence of late-onset toxicities.
  • Comparison of dose-limiting toxicity (DLT) incidence across different bortezomib dose groups.

Main Results:

  • Over 13,000 toxicities were recorded, with 46% of first DLTs and 88% of dose reductions/discontinuations occurring after the first cycle.
  • At the approved dose of 1.3 mg/m², the cumulative incidence of DLT exceeded 50%.
  • Nearly 40% of patients required dose reduction or treatment discontinuation due to toxicity at the approved dose.

Conclusions:

  • The approved dose of bortezomib surpasses the conventional DLT rate threshold (20-33%), indicating potential tolerability issues.
  • Retrospective analysis of clinical trial data is valuable for optimizing MTA doses.
  • Future dose-finding studies for MTAs must incorporate late-onset toxicity assessments to establish tolerable doses for efficacy and comparative trials.