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

Dosage Regimens: Designs and Approaches01:28

Dosage Regimens: Designs and Approaches

107
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...
107
Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations01:15

Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations

67
Gentamicin, an aminoglycoside antibiotic, is commonly administered via intermittent intravenous infusion to treat severe infections. An intermittent one-hour infusion of gentamicin, administered at eight-hour intervals, allows for precise control of plasma drug concentrations, minimizing toxicity while ensuring therapeutic efficacy. Pharmacokinetic principles govern the dynamics of plasma concentrations and can be mathematically described using specific equations.The plasma drug concentration...
67
Determination of Multiple Dosing Parameters: Loading and Maintenance Doses01:25

Determination of Multiple Dosing Parameters: Loading and Maintenance Doses

63
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...
63
Dosage Regimens: Partial Pharmacokinetic Parameters01:01

Dosage Regimens: Partial Pharmacokinetic Parameters

46
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...
46
Bioavailability Study Design: Single Versus Multiple Dose Studies01:11

Bioavailability Study Design: Single Versus Multiple Dose Studies

59
Bioavailability studies are essential for understanding how a drug is absorbed, distributed, metabolized, and excreted in the body. These studies assess the extent and rate at which the active pharmaceutical agent becomes available at the site of action. The design of bioavailability studies can involve single-dose or multiple-dose regimens, each with distinct advantages and limitations.Single-dose studies are the preferred approach due to their simplicity and reduced drug exposure for...
59
Dosage Regimen Designs: Nomograms and Tabulations01:23

Dosage Regimen Designs: Nomograms and Tabulations

59
Nomograms and tabulations are vital tools used by clinicians to design accurate and individualized dosage regimens. These instruments provide a straightforward method for adjusting dosages based on individual patient characteristics, including age, weight, and physiological condition. The foundation of a drug's nomogram is population pharmacokinetic data collected and analyzed using specific models. This data simplifies complex equations, presenting them diagrammatically or tabularly for easy...
59

You might also read

Related Articles

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

Sort by
Same author

A phase 1 dose-finding and pharmacokinetic study of acasunlimab alone or in combination with pembrolizumab in Japanese patients with advanced or metastatic solid tumors.

International journal of clinical oncology·2026
Same author

Three-year follow-up of epcoritamab therapy in Japanese patients with relapsed/refractory follicular lymphoma in EPCORE NHL-3.

International journal of hematology·2026
Same author

Subcutaneous epcoritamab monotherapy in Japanese patients with relapsed or refractory follicular lymphoma: primary results of the EPCORE NHL-3 trial.

Leukemia & lymphoma·2025
Same author

Efficacy and safety of epcoritamab in Japanese patients with relapsed or refractory diffuse large B-cell lymphoma: 3-year follow-up from the EPCORE NHL-3 trial.

International journal of clinical oncology·2025
Same author

UV-B Irradiation Does Not Promote Flowering in <i>Arabidopsis</i> Despite Increased <i>FT</i> Expression.

Plant direct·2025
Same author

Enhanced effect of the immunosuppressive soluble HLA-G2 homodimer by site-specific PEGylation.

Scientific reports·2025

Related Experiment Video

Updated: Nov 10, 2025

A Workflow for Lipid Nanoparticle LNP Formulation Optimization using Designed Mixture-Process Experiments and Self-Validated Ensemble Models SVEM
13:54

A Workflow for Lipid Nanoparticle LNP Formulation Optimization using Designed Mixture-Process Experiments and Self-Validated Ensemble Models SVEM

Published on: August 18, 2023

5.3K

Bayesian optimization design for finding a maximum tolerated dose combination in phase I clinical trials.

Ami Takahashi1, Taiji Suzuki2

  • 1Tokyo Institute of Technology, School of Computing, Meguro-ku, Tokyo, Japan.

The International Journal of Biostatistics
|April 5, 2021
PubMed
Summary

This study introduces a novel Bayesian optimization design for finding the maximum tolerated dose combination in clinical trials. This method efficiently identifies optimal drug combinations, improving patient treatment strategies.

Keywords:
Bayesian optimizationcombination therapymaximum tolerated dosenonparametric methodphase I clinical trials

More Related Videos

Diagonal Method to Measure Synergy Among Any Number of Drugs
12:08

Diagonal Method to Measure Synergy Among Any Number of Drugs

Published on: June 21, 2018

19.1K
Optimization of Processing of Tiebangchui with Highland Barley Wine Based on the Box-Behnken Design Combined with the Entropy Method
09:12

Optimization of Processing of Tiebangchui with Highland Barley Wine Based on the Box-Behnken Design Combined with the Entropy Method

Published on: May 19, 2023

1.0K

Related Experiment Videos

Last Updated: Nov 10, 2025

A Workflow for Lipid Nanoparticle LNP Formulation Optimization using Designed Mixture-Process Experiments and Self-Validated Ensemble Models SVEM
13:54

A Workflow for Lipid Nanoparticle LNP Formulation Optimization using Designed Mixture-Process Experiments and Self-Validated Ensemble Models SVEM

Published on: August 18, 2023

5.3K
Diagonal Method to Measure Synergy Among Any Number of Drugs
12:08

Diagonal Method to Measure Synergy Among Any Number of Drugs

Published on: June 21, 2018

19.1K
Optimization of Processing of Tiebangchui with Highland Barley Wine Based on the Box-Behnken Design Combined with the Entropy Method
09:12

Optimization of Processing of Tiebangchui with Highland Barley Wine Based on the Box-Behnken Design Combined with the Entropy Method

Published on: May 19, 2023

1.0K

Area of Science:

  • Clinical Pharmacology
  • Biostatistics
  • Drug Development

Background:

  • Combination therapies are crucial for treating resistant cancers, but determining optimal doses is challenging due to complex drug interactions.
  • Existing parametric models for dose-finding in Phase I trials rely on strong assumptions that may not hold for drug combinations.
  • A standardized method for identifying the maximum tolerated dose combination is currently lacking.

Purpose of the Study:

  • To propose a novel Bayesian optimization design for identifying a single maximum tolerated dose combination.
  • To address the limitations of existing methods in handling complex drug-drug interactions and limited prior information.
  • To develop a more efficient and reliable approach for dose-finding in combination therapy trials.

Main Methods:

  • A Bayesian optimization design is proposed, balancing exploration and exploitation for dose selection.
  • The design utilizes a nonparametric estimation of the dose-toxicity relationship.
  • The proposed method was evaluated through simulations against established designs like the Bayesian optimal interval and partial-ordering continual reassessment method.

Main Results:

  • Simulation results indicate the proposed Bayesian optimization design performs well in terms of selecting the correct dose combination.
  • The design demonstrates effective dose allocation, minimizing patient exposure to overly toxic regimens.
  • The method achieved global optima with fewer evaluations compared to existing approaches.

Conclusions:

  • The proposed Bayesian optimization design offers a robust and efficient solution for identifying maximum tolerated dose combinations.
  • This approach has significant potential to enhance the development of effective combination therapies in clinical trials.
  • Further application of this design could lead to improved treatment strategies for patients with limited options.