Pathophysiological Influences on Pharmacokinetics and Pharmacodynamics, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics".

Deadline for manuscript submissions: 31 October 2026 | Viewed by 1010

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Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil
Interests: placental pharmacokinetic; pregnancy; high-risk pregnancy; infection in obstetrics
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Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil
Interests: clinical pharmacokinetics; pharmacometrics; PBPK; in vitro drug metabolism
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Guest Editor
School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil
Interests: clinical pharmacology; model-informed precision dosing; pharmacokinetics; drug-disease interactions
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Special Issue Information

Dear Colleagues,

Pharmaceutics is excited to announce a Special Issue on “Pathophysiological Influences on Pharmacokinetics and Pharmacodynamics, 2nd Edition”. This Special Issue aims to explore the latest advancements in PK and PD research across a diverse range of pathophysiological conditions.

Understanding how both diseases and physiological changes alter drug disposition is essential for tailoring pharmacological treatments to individual patients. Such insights are crucial to ensuring that therapies are both safe and effective. Disease states—such as infections, inflammatory states, and acute and chronic diseases—can significantly impact drug absorption, distribution, metabolism, and excretion, leading to variability in drug response that may result in adverse effects or therapeutic failure.

A key objective of clinical pharmacology is to promote individualized pharmacotherapy by identifying the factors that contribute to variability in drug response, with a particular focus on PK and PD. Many conditions, including bacterial, viral, fungal, and protozoal infections, chronic diseases like type 2 diabetes, neoplasms, autoimmune disorders, and physiological states such as pregnancy, are known to influence drug disposition. However, there remains a notable gap in the literature regarding the characterization of drug-metabolizing enzymes and transporters in both disease states and physiological conditions, particularly by in vivo activity markers.

This Special Issue seeks to address these gaps by highlighting recent progress in understanding the impact of both pathophysiological and physiological factors on drug kinetics and dynamics. Potential topics of interest include, but are not limited to, the following:

  • Characterization of drug kinetic disposition in patients with specific pathophysiological or physiological conditions;
  • Comparisons of PK and/or PD between healthy individuals and those with diseases or altered physiological states;
  • Exploration of how disease states and physiological conditions can modify drug absorption, distribution, metabolism, and excretion;
  • Impact of comorbidities and physiological changes on pharmacotherapy outcomes;
  • Optimization of drug therapy in patients with altered physiological states, including pregnancy;
  • Advances in PBPK modeling that account for pathophysiological and physiological influences.

We invite researchers from academia, government agencies, and industry to submit their work to this Special Issue. Each submission will undergo rigorous peer review and be edited by leading experts in the field to ensure the highest standards of quality and relevance. If you are interested in further discussion, please feel free to contact the Guest Editors.

Dr. Geraldo Duarte
Dr. Fernanda de Lima Moreira
Dr. Jhohann Richard de Lima Benzi
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • drug–disease interactions
  • pharmacokinetics
  • pharmacodynamics
  • pharmacotherapy

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Published Papers (1 paper)

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Research

29 pages, 2659 KB  
Article
Model-Based Virtual Clinical Trial Reveals Renal Impairment and Body Size as Key Determinants of Pharmacokinetic Variability and Drug-Drug Interaction Risk in Propranolol Therapy
by Lara Marques and Nuno Vale
Pharmaceutics 2026, 18(6), 636; https://doi.org/10.3390/pharmaceutics18060636 - 22 May 2026
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Abstract
Background/Objectives: Propranolol (PROP) is a non-selective β-blocker widely prescribed for cardiovascular and neurological disorders. Its pharmacokinetics (PK) are highly variable, and co-administration with omeprazole (OME), a CYP2C19 substrate and inhibitor, may alter systemic exposure. Herein, this study aimed to investigate factors influencing PROP [...] Read more.
Background/Objectives: Propranolol (PROP) is a non-selective β-blocker widely prescribed for cardiovascular and neurological disorders. Its pharmacokinetics (PK) are highly variable, and co-administration with omeprazole (OME), a CYP2C19 substrate and inhibitor, may alter systemic exposure. Herein, this study aimed to investigate factors influencing PROP PK variability and evaluate the effect of OME coadministration using physiologically based pharmacokinetic (PBPK) modeling and population PK (popPK) analysis. Methods: PBPK models for PROP and OME were developed and validated against published data. DDI simulations were conducted across clinically relevant dosing regimens. A two-period fixed-sequence virtual trial of 125 subjects was simulated with PROP alone and PROP combined with OME. Population PK (popPK) analysis was performed on simulated plasma concentration data to identify covariates affecting PROP disposition and quantify DDI magnitude. Results: PBPK models were successfully developed and validated. PROP disposition was best described by a two-compartment model with linear elimination. Health status was found to influence clearance, and body surface area (BSA) affected the central volume of distribution. Co-administration with OME increased PROP exposure, with larger effects in patients with renal impairment. Simulated plasma concentrations remained below established toxicity thresholds. Conclusions: Virtual clinical trials integrating PBPK and popPK modeling provide a robust approach to identifying key determinants of PK variability and DDI risk. Although these findings were not directly translated to clinical observations, this helps identify sources of PK variability in PROP treatment settings and factors that may intensify its interaction with OME, thereby supporting model-informed precision dosing to enhance safety and efficacy. Full article
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