Advances in Pharmacokinetics and Drug Interactions

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

Deadline for manuscript submissions: 20 October 2024 | Viewed by 1026

Special Issue Editors


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Guest Editor
Center for Pharmacometrics & Systems Pharmacology, Department of Pharmaceutics Lake Nona (Orlando), University of Florida, 6550 Sanger Road, Office 464, Orlando, FL 32827, USA
Interests: the development and application of disease-drug-trial models in the area of chronic progressive diseases; special patient populations; drug-drug interactions; pharmacokinetics

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Guest Editor
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL, USA
Interests: special populations; pharmacometrics; quantitative pharmacology
Special Issues, Collections and Topics in MDPI journals

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Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas (UNIFAL-MG), Alfenas 371300-001, Brazil
Interests: drug toxicology; toxicological analysis; pharmacokinetics; pharmacodynamics; validation of methods

Special Issue Information

Dear Colleagues,

Pharmaceutics is announcing this Special Issue on “Advances in Pharmacokinetics and Drug Interactions” with the goal of exploring the latest developments and advancements in pharmacokinetics (PK), quantitative pharmacology, and drug–drug interactions. Great strides have been made towards furthering our understanding of pharmacokinetics and drug interactions with the development of more advanced modeling and simulation approaches. Quantitative pharmacology approaches are helpful for understanding drug absorption, distribution, metabolism, and excretion, predicting drug concentrations, assessing drug–drug interactions, and understanding the variability in drug response. By integrating PK models with pharmacodynamic (PD) models, we can further forecast drug effects on biomarkers or clinical endpoints.

Drug–drug interactions (DDIs) are a major concern in drug development and clinical practice. DDIs can escalate the frequency and severity of adverse events or elevate the risk of treatment failure. Early prediction of the likelihood and the magnitude of DDIs has become part of the assessment of a new drug’s safety profile during drug development. Mechanistic and physiological approaches enable researchers to anticipate drug behavior across patient populations. In this context, physiologically based pharmacokinetic modeling has been extensively used to assess DDIs and support new drug applications to regulatory agencies. Subsequently, simulations allow the identification of patient subgroups at a higher risk of therapeutic failure, drug interactions, or safety concerns. Once these differences are characterized, the PK model can be linked to response models to assess whether dose adjustments are needed and, in this case, to optimize dosing strategies. Further improvements in pharmacokinetics and drug interactions may enhance pharmacological efficacy, safety, and patient outcomes, enabling more customized and effective treatment interventions.

This Special Issue—“Advances in Pharmacokinetics and Drug Interactions”—aims to showcase recent progress in pharmacokinetics and drug interactions to explore drug behavior and therapeutic results. Potential topics include but are not limited to:

  • PK(/PD), PBPK, QSP models of drugs;
  • Optimization of dosing regimens;
  • Static models to investigate DDI potential and mechanistic models to investigate and confirm DDI potential;
  • In vitro–in vivo extrapolation in the context of DDI;
  • Mechanisms of drug–drug or drug–xenobiotic interactions;
  • Quantitative pharmacology approaches.

We cordially invite researchers from academia, industry, and government agencies working in related fields to submit their work. The Special Issue will undergo rigorous review and editing by leading experts in pharmacokinetics and drug metabolism, ensuring that the articles meet the highest standards of quality and relevance.

Based on your expertise in the field, we would be honored if you would consider our invitation. If you are interested in discussing the Issue further, please feel free to contact the guest editors:

Prof. Dr. Stephan Schmidt
Prof. Dr. Natalia V. De Moraes
Prof. Dr. Vanessa Bergamin Boralli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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-blind 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

  • pharmacokinetics
  • drug interactions
  • PBPK modeling
  • drug delivery systems
  • personalized medicine

Published Papers (1 paper)

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Research

25 pages, 5791 KiB  
Article
Applying Physiologically Based Pharmacokinetic Modeling to Interpret Carbamazepine’s Nonlinear Pharmacokinetics and Its Induction Potential on Cytochrome P450 3A4 and Cytochrome P450 2C9 Enzymes
by Xuefen Yin, Brian Cicali, Leyanis Rodriguez-Vera, Viera Lukacova, Rodrigo Cristofoletti and Stephan Schmidt
Pharmaceutics 2024, 16(6), 737; https://doi.org/10.3390/pharmaceutics16060737 - 30 May 2024
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Abstract
Carbamazepine (CBZ) is commonly prescribed for epilepsy and frequently used in polypharmacy. However, concerns arise regarding its ability to induce the metabolism of other drugs, including itself, potentially leading to the undertreatment of co-administered drugs. Additionally, CBZ exhibits nonlinear pharmacokinetics (PK), but the [...] Read more.
Carbamazepine (CBZ) is commonly prescribed for epilepsy and frequently used in polypharmacy. However, concerns arise regarding its ability to induce the metabolism of other drugs, including itself, potentially leading to the undertreatment of co-administered drugs. Additionally, CBZ exhibits nonlinear pharmacokinetics (PK), but the root causes have not been fully studied. This study aims to investigate the mechanisms behind CBZ’s nonlinear PK and its induction potential on CYP3A4 and CYP2C9 enzymes. To achieve this, we developed and validated a physiologically based pharmacokinetic (PBPK) parent–metabolite model of CBZ and its active metabolite Carbamazepine-10,11-epoxide in GastroPlus®. The model was utilized for Drug–Drug Interaction (DDI) prediction with CYP3A4 and CYP2C9 victim drugs and to further explore the underlying mechanisms behind CBZ’s nonlinear PK. The model accurately recapitulated CBZ plasma PK. Good DDI performance was demonstrated by the prediction of CBZ DDIs with quinidine, dolutegravir, phenytoin, and tolbutamide; however, with midazolam, the predicted/observed DDI AUClast ratio was 0.49 (slightly outside of the two-fold range). CBZ’s nonlinear PK can be attributed to its nonlinear metabolism caused by autoinduction, as well as nonlinear absorption due to poor solubility. In further applications, the model can help understand DDI potential when CBZ serves as a CYP3A4 and CYP2C9 inducer. Full article
(This article belongs to the Special Issue Advances in Pharmacokinetics and Drug Interactions)
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