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Pharmaceutics
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Novel Approaches for Optimizing Pharmacotherapy Based on Recent Pharmacokinetic, Pharmacodynamic,...
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Novel Approaches for Optimizing Pharmacotherapy Based on Recent Pharmacokinetic, Pharmacodynamic, and Pharmacogenetic Developments

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

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 2526

Special Issue Editors

Prof. Dr. Elżbieta Wyska

E-Mail Website
Guest Editor
Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland
Interests: pharmacokinetics; pharmacodynamics; PK/PD modeling; PBPK modeling; bioanalysis; PDE inhibitors; inflammation
Dr. Małgorzata Szafarz

E-Mail Website
Guest Editor
Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Medyczna 9, PL 30-688 Cracow, Poland
Interests: preclinical pharmacokinetic assessment of pharmacologically active compounds; estimation of hepatic clearance; isolated hepatocytes; isolated perfused liver model; bioanalysis; LC-MS/MS; drug–drug interactions; clinical pharmacokinetics of cytostatic and antimicrobial drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Drug development is a complex, costly, and time-consuming process. Even if the number of new drugs approved each year is increasing, slow progress is observed in approval of drugs for some disorders, such as neurological or lifestyle diseases, with greater emphasis being placed on anticancer drugs and biologics. Therefore, we should adopt the most effective use of existing drugs supported by innovative analytical, computational, and genetic-based methods.

This Special Issue presents the advances in the optimization of pharmacotherapy observed in recent years as a result of the current progress in pharmacokinetics and pharmacodynamics, the introduction of new sampling and analytical techniques, and the implementation of pharmacogenetic testing in clinical practice. Equally important in this area is the introduction of novel biomarkers of drug response and disease progression, advanced computer-based methods, and PK/PD models that can be used to select an appropriate dose and dosage scheme for an individual patient.

Prof. Dr. Elżbieta Wyska
Dr. Małgorzata Szafarz
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

  • dosage individualization
  • TDM
  • pharmacogenetics
  • PK/PD modeling
  • simulations
  • software
  • biomarkers

Published Papers (3 papers)

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Research

8 pages, 595 KiB  
Article
Casgevy: Innovative Medicinal Products Require Innovative Approaches to Regulatory Assessment
by Essam Kerwash and John D. Johnston
Pharmaceutics 2024, 16(7), 906; https://doi.org/10.3390/pharmaceutics16070906 (registering DOI) - 6 Jul 2024
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Abstract
Casgevy (exa-cel) is an autologous cellular therapy modified ex vivo by a CRISPR-Cas9-mediated gene-editing technology. For Casgevy to be granted the indication in transfusion-dependent β-thalassemia, one single-arm trial was submitted which was not amenable to conventional statistical analysis of ‘effect of cause’. Therefore, [...] Read more.
Casgevy (exa-cel) is an autologous cellular therapy modified ex vivo by a CRISPR-Cas9-mediated gene-editing technology. For Casgevy to be granted the indication in transfusion-dependent β-thalassemia, one single-arm trial was submitted which was not amenable to conventional statistical analysis of ‘effect of cause’. Therefore, an analysis was conducted on the basis of ‘cause of effect’ making use of the scheme described by Toulmin coupled to an analysis of causal inference. Based on the current data within the submitted study: subjects with transfusion-dependent β-thalassemia no longer needed a red blood cell transfusion with a 93-percent probability if and only if administered Casgevy; PNS = 93%. It is acknowledged that unknown elements of safety may yet be revealed by long-term follow-up of recipients of Casgevy. Its durability of efficacy is, at present, also an unknown that may also be ascertained by long-term follow-up of recipients. The limitations of a causal analysis are related to assumptions of the proposed causal structure which may not capture the complexity of the real world. Overall, the claim that Casgevy is indicated to treat people with transfusion-dependent β-thalassemia is considered to be supported by the results of the submitted study; the benefit–risk evaluation of Casgevy is found to be positive. Full article
(This article belongs to the Special Issue Novel Approaches for Optimizing Pharmacotherapy Based on Recent Pharmacokinetic, Pharmacodynamic, and Pharmacogenetic Developments)
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15 pages, 782 KiB  
Article
Serum Concentration–Dose Relationship and Modulation Factors in Children and Adolescents Treated with Fluvoxamine
by Regina Taurines, Gesa Kunkel, Stefanie Fekete, Jörg M. Fegert, Christoph Wewetzer, Christoph U. Correll, Kristian Holtkamp, Isabel Böge, Tobias Johann Renner, Hartmut Imgart, Maike Scherf-Clavel, Peter Heuschmann, Manfred Gerlach, Marcel Romanos and Karin Egberts
Pharmaceutics 2024, 16(6), 772; https://doi.org/10.3390/pharmaceutics16060772 - 6 Jun 2024
Viewed by 403
Abstract
Introduction: Fluvoxamine is used in children and adolescents (‘youths’) for treating obsessive compulsive disorder (OCD) but also off-label for depressive and anxiety disorders. This study aimed to investigate the relationship between fluvoxamine dose and serum concentrations, independent correlates of fluvoxamine concentrations, and a [...] Read more.
Introduction: Fluvoxamine is used in children and adolescents (‘youths’) for treating obsessive compulsive disorder (OCD) but also off-label for depressive and anxiety disorders. This study aimed to investigate the relationship between fluvoxamine dose and serum concentrations, independent correlates of fluvoxamine concentrations, and a preliminary therapeutic reference range (TRR) for youths with OCD and treatment response. Methods: Multicenter naturalistic data of a therapeutic drug monitoring service, as well as prospective data of the ‘TDM Vigil study’ (EudraCT 2013-004881-33), were analyzed. Patient and treatment characteristics were assessed by standardized measures, including Clinical Global Impressions—Severity (CGI-S) and —Change (CGI-I), with CGI-I of much or very much improved defining treatment response and adverse drug reactions using the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale. Multivariable regression analysis was used to evaluate the influence of sex, age, body weight, body mass index (BMI), and fluvoxamine dose on fluvoxamine serum concentrations. Results: The study included 70 youths (age = 6.7–19.6 years, OCD = 78%, mean fluvoxamine dose = 140.4 (range = 25–300) mg/d). A weak positive correlation between daily dose and steady-state trough serum concentrations was found (rs = 0.34, p = 0.004), with dose variation explaining 16.2% of serum concentration variability. Multivariable correlates explaining 25.3% of the variance of fluvoxamine concentrations included higher fluvoxamine dose and lower BMI. Considering responders with OCD, the estimated TRR for youths was 55–371 ng/mL, exceeding the TRR for adults with depression of 60–230 ng/mL. Discussion: These preliminary data contribute to the definition of a TRR in youth with OCD treated with fluvoxamine and identify higher BMI as a moderator of lower fluvoxamine concentrations. Full article
(This article belongs to the Special Issue Novel Approaches for Optimizing Pharmacotherapy Based on Recent Pharmacokinetic, Pharmacodynamic, and Pharmacogenetic Developments)
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19 pages, 5575 KiB  
Article
Transcriptomics- and Genomics-Guided Drug Repurposing for the Treatment of Vesicular Hand Eczema
by Fieke M. Rosenberg, Zoha Kamali, Angelique N. Voorberg, Thijs H. Oude Munnink, Peter J. van der Most, Harold Snieder, Ahmad Vaez and Marie L. A. Schuttelaar
Pharmaceutics 2024, 16(4), 476; https://doi.org/10.3390/pharmaceutics16040476 - 30 Mar 2024
Viewed by 1354
Abstract
Vesicular hand eczema (VHE), a clinical subtype of hand eczema (HE), showed limited responsiveness to alitretinoin, the only approved systemic treatment for severe chronic HE. This emphasizes the need for alternative treatment approaches. Therefore, our study aimed to identify drug repurposing opportunities for [...] Read more.
Vesicular hand eczema (VHE), a clinical subtype of hand eczema (HE), showed limited responsiveness to alitretinoin, the only approved systemic treatment for severe chronic HE. This emphasizes the need for alternative treatment approaches. Therefore, our study aimed to identify drug repurposing opportunities for VHE using transcriptomics and genomics data. We constructed a gene network by combining 52 differentially expressed genes (DEGs) from a VHE transcriptomics study with 3 quantitative trait locus (QTL) genes associated with HE. Through network analysis, clustering, and functional enrichment analyses, we investigated the underlying biological mechanisms of this network. Next, we leveraged drug–gene interactions and retrieved pharmaco-transcriptomics data from the DrugBank database to identify drug repurposing opportunities for (V)HE. We developed a drug ranking system, primarily based on efficacy, safety, and practical and pricing factors, to select the most promising drug repurposing candidates. Our results revealed that the (V)HE network comprised 78 genes that yielded several biological pathways underlying the disease. The drug–gene interaction search together with pharmaco-transcriptomics lookups revealed 123 unique drug repurposing opportunities. Based on our drug ranking system, our study identified the most promising drug repurposing opportunities (e.g., vitamin D analogues, retinoids, and immunomodulating drugs) that might be effective in treating (V)HE. Full article
(This article belongs to the Special Issue Novel Approaches for Optimizing Pharmacotherapy Based on Recent Pharmacokinetic, Pharmacodynamic, and Pharmacogenetic Developments)
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