Pharmacokinetics and Pharmacodynamics of Therapeutic Biologics

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Drug Discovery, Development and Delivery".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 2914

Special Issue Editor

School of Pharmacy, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong
Interests: pharmacokinetics and pharmacodynamics of erythropoiesis-stimulating agents; pharmacokinetics and pharmacodynamics of therapeutic mAb; pharmacokinetic modeling; pharmacokinetic-pharmacodynamic modeling; model-informed drug development

Special Issue Information

Dear Colleagues,

The Special Issue, “Pharmacokinetics and Pharmacodynamics of Therapeutic Biologics”, will focus on the pharmacokinetics and pharmacodynamics of biologics (proteins and peptides) such as therapeutic growth factors and antibody-based therapeutics, including monoclonal antibodies, bispecific antibodies, antibody–drug conjugates, fragment antibodies, etc.

Therapeutic biologics are an important class of drugs used to treat a wide range of diseases. They have some unique pharmacokinetics (PK) and pharmacodynamics (PD) properties due to their molecular complexity. This Special Issue aims to provide an up-to-date overview of the latest research in this area, highlighting advances in our understanding of the PK and PD of therapeutic biologics, and identifying key areas for future research.

This Special Issue is open for basic to clinical research, or a multidisciplinary approach, and will also cover original articles and reviews on the following topics:

  • Determinants of PK and PD of biologics: This subcategory will focus on the study of various factors such as size, molecular structure, route of administrations, formulation, target binding, immune response, etc., on the PK and PD on biologics.
  • PK/PD and PBPK modeling: This subcategory will focus on the use of mathematical models to describe the PK and PD of biologics, and to optimize dosing regimens for different patient populations.
  • Clinical pharmacology: This subcategory will examine the results of clinical trials investigating the PK, PD, safety, and tolerability of biologics.
  • Novel technologies: This subcategory will explore the latest technological advances in the study of PK and PD of biologics.

Dr. Xiaoyu Yan
Guest Editor

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Keywords

  • pharmacokinetics
  • pharmacodynamics
  • PK/PD modeling
  • PBPK modeling
  • mAb
  • ADC
  • pharmacometrics

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Published Papers (2 papers)

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Research

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12 pages, 1770 KiB  
Article
Population Pharmacokinetic Model of Adalimumab Based on Prior Information Using Real World Data
by Silvia Marquez-Megias, Ricardo Nalda-Molina, Patricio Más-Serrano and Amelia Ramon-Lopez
Biomedicines 2023, 11(10), 2822; https://doi.org/10.3390/biomedicines11102822 - 18 Oct 2023
Cited by 1 | Viewed by 1333
Abstract
Adalimumab is a fully human monoclonal antibody used for the treatment of inflammatory bowel disease (IBD). Due to its considerably variable pharmacokinetics and the risk of developing antibodies against adalimumab, it is highly recommended to use a model-informed precision dosing approach. The aim [...] Read more.
Adalimumab is a fully human monoclonal antibody used for the treatment of inflammatory bowel disease (IBD). Due to its considerably variable pharmacokinetics and the risk of developing antibodies against adalimumab, it is highly recommended to use a model-informed precision dosing approach. The aim of this study is to develop a population pharmacokinetic (PopPK) model of adalimumab for patients with IBD based on a literature model (reference model) to be used in the clinical setting. A retrospective observational study with 54 IBD patients was used to develop two different PopPK models based on the reference model. One of the developed models estimated the pharmacokinetic population parameters (estimated model), and the other model incorporated informative priors (prior model). The models were evaluated with bias and imprecision. Clinical impact was also assessed, evaluating the differences in dose interventions. The developed models included the albumin as a continuous covariate on apparent clearance. The prior model was superior to the estimated model in terms of bias, imprecision and clinical impact on the target population. In conclusion, the prior model adequately characterized adalimumab PK in the studied population and was better than the reference model in terms of predictive performance and clinical impact. Full article
(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics of Therapeutic Biologics)
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Review

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19 pages, 1701 KiB  
Review
Upholding or Breaking the Law of Superposition in Pharmacokinetics
by Malaz Yousef, Jaime A. Yáñez, Raimar Löbenberg and Neal M. Davies
Biomedicines 2024, 12(8), 1843; https://doi.org/10.3390/biomedicines12081843 - 13 Aug 2024
Viewed by 881
Abstract
The law of superposition underpins first-order linear pharmacokinetic relationships. Most drugs, therefore, after a single dose can be described by first-order or linear processes, which can be superposed to understand multiple-dose regimen behavior. However, there are a number of situations where drugs could [...] Read more.
The law of superposition underpins first-order linear pharmacokinetic relationships. Most drugs, therefore, after a single dose can be described by first-order or linear processes, which can be superposed to understand multiple-dose regimen behavior. However, there are a number of situations where drugs could display behaviors after multiple dosing that leads to capacity-limited or saturation non-linear kinetics and the law of superposition is overruled. This review presents a practical guide to understand the equations and calculations for single and multiple-dosing regimens after intravenous and oral administration. It also provides the pharmaceutical basis for saturation in ADME processes and the consequent changes in the area under the concentration–time curve, which represents drug exposure that can lead to the modulation of efficacy and/or toxic effects. The pharmacokineticist must implicitly understand the principles of superposition, which are a central tenet of drug behavior and disposition during drug development. Full article
(This article belongs to the Special Issue Pharmacokinetics and Pharmacodynamics of Therapeutic Biologics)
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