Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.9
4.9
Journals
Pharmaceutics
Special Issues
Advances in ADME for Drug Discovery
share announcement

Advances in ADME for Drug Discovery

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

Deadline for manuscript submissions: closed (10 January 2025) | Viewed by 2363

Special Issue Editors

Prof. Dr. José Luiz Costa

E-Mail Website
Guest Editor
Faculty of Pharmaceutical Sciences, University of Campinas (UNICAMP), Campinas 13083-871, Brazil
Interests: toxicology; analytical toxicology; forensic and clinical toxicology; mass spectrometry; chromatography
Dr. Natalicia De Jesus Antunes

E-Mail Website
Guest Editor
Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas 13083-970, Brazil
Interests: pharmacology; toxicology; pharmacokinetics; metabolism; PBPK modeling; PK/PD modeling; bioanalysis; mass spectrometry; chromatography

Special Issue Information

Dear Colleagues,

Drug discovery investigations require a profound understanding of the absorption, distribution, metabolism, and excretion (ADME) of pharmaceutical compounds. The absorption kinetics and fate of a drug in the human body play pivotal roles in determining its efficacy and safety profile. Drug–drug interactions (DDI) further complicate this landscape, potentially altering systemic exposure and introducing unexpected side effects.

Our forthcoming Special Issue aims to delve into the crucial aspects of ADME, shedding light on its significance in contemporary drug discovery. As evidenced by recent research, the identification and development of potential drug candidates involve navigating through various challenges, including pharmacokinetics, drug interactions, and safety considerations. ADME properties have emerged as decisive factors influencing the success or failure of promising bioactive compounds.

This Special Issue invites contributions encompassing diverse methodologies, from in vitro and in vivo experiments to in silico modeling and simulation approaches. We encourage submissions of original and review articles showcasing advancements in drug metabolism and pharmacokinetics (DMPK) and clinical pharmacology, particularly in the evaluation and prediction of DDIs. By exploring these facets, we aim to foster a comprehensive understanding of ADME properties, ultimately facilitating the expedited and effective development of novel therapeutic agents.

We look forward to receiving your contributions.

Prof. Dr. José Luiz Costa
Dr. Natalicia De Jesus Antunes
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
  • absorption
  • bioavailability
  • metabolism
  • PBPK modelling
  • PK/PD modelling
  • drug–drug interaction

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (2 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

28 pages, 6517 KiB  
Article
Evaluation of Violacein Metabolic Stability and Metabolite Identification in Human, Mouse, and Rat Liver Microsomes
by Debora Bressanim de Aquino Calemi, Alexandre Barcia Godoi, Giulia Minuti, Fausto Carnevale Neto, Gabriel Felipe Hispagnol, Alan Cesar Pilon, Jose Luiz Costa, Stephen Hyslop and Natalicia de Jesus Antunes
Pharmaceutics 2025, 17(5), 601; https://doi.org/10.3390/pharmaceutics17050601 - 2 May 2025
Viewed by 195
Abstract
Background: Malaria significantly impacts the health of populations living in poverty and vulnerable conditions. Resistance to current antimalarial drugs remains a major challenge and highlights the urgent need for novel, effective, and safer therapies. Violacein, a purple pigment, has demonstrated potent antiplasmodial [...] Read more.
Background: Malaria significantly impacts the health of populations living in poverty and vulnerable conditions. Resistance to current antimalarial drugs remains a major challenge and highlights the urgent need for novel, effective, and safer therapies. Violacein, a purple pigment, has demonstrated potent antiplasmodial activity, making it a promising antimalarial candidate. However, to date, no in vitro metabolism studies of violacein have been published. In this study, the metabolic stability of violacein was evaluated using human (HLMs), mouse (MLMs), and rat (RLMs) liver microsomes and the metabolites generated by HLMs and RLMs were assessed. Methods: Liquid chromatography quadrupole mass spectrometry (LC-MS/MS) was used to investigate the metabolic stability of violacein, while liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was used to identify the metabolites. In silico analyses were used to support in vitro metabolite identification by providing insights into potential metabolic pathways and predicting metabolite structures, thereby enhancing the accuracy and efficiency of the identification process. Results: The half-life (t1/2) for violacein in RLMs, MLMs, and HLMs was 36, 81, and 216 min, respectively. The in vitro intrinsic clearance (CLint, in vitro) values were 38.4, 17.0, and 6.4 µL/min/mg for RLMs, MLMs, and HLMs, respectively, while the in vivo intrinsic clearance (CLint, in vivo) was 93.7, 67.0, and 6.6 mL/min/kg, respectively. A slow elimination profile was observed in HLMs followed by MLMs, with rapid elimination in RLMs, indicating greater stability of violacein in HLMs and MLMs when compared with RLMs. Four violacein metabolites were identified in HLMs and RLMs, two of which were formed by phase I metabolism, one by phase II metabolism, and one by phase I + II metabolism. Conclusions: This study provides the first published analysis of the metabolic stability of violacein. Full article
(This article belongs to the Special Issue Advances in ADME for Drug Discovery)
►▼ Show Figures

Figure 1

13 pages, 3288 KiB  
Article
Identification of the Biotransformation Pathways of a Potential Oral Male Contraceptive, 11β-Methyl-19-Nortestosterone (11β-MNT) and Its Prodrugs: An In Vitro Study Highlights the Contribution of Polymorphic Intestinal UGT2B17
by Namrata Bachhav, Dilip Kumar Singh, Diana L. Blithe, Min S. Lee and Bhagwat Prasad
Pharmaceutics 2024, 16(8), 1032; https://doi.org/10.3390/pharmaceutics16081032 - 2 Aug 2024
Cited by 1 | Viewed by 1351
Abstract
11β-Methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) is a prodrug of 11β-MNT and is being considered as a promising male oral contraceptive candidate in clinical development. However, the oral administration of 11β-MNTDC exhibits an ~200-fold lower serum concentration of 11β-MNT compared to 11β-MNTDC, resulting in the poor [...] Read more.
11β-Methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) is a prodrug of 11β-MNT and is being considered as a promising male oral contraceptive candidate in clinical development. However, the oral administration of 11β-MNTDC exhibits an ~200-fold lower serum concentration of 11β-MNT compared to 11β-MNTDC, resulting in the poor bioavailability of 11β-MNT. To elucidate the role of the first-pass metabolism of 11β-MNT in its poor bioavailability, we determined the biotransformation products of 11β-MNT and its prodrugs in human in vitro models. 11β-MNT and its two prodrugs 11β-MNTDC and 11β-MNT undecanoate (11β-MNTU) were incubated in cryopreserved human hepatocytes (HHs) and subjected to liquid chromatography–high resolution tandem mass spectrometry analysis, which identified ten 11β-MNT biotransformation products with dehydrogenated and glucuronidation (11β-MNTG) metabolites being the major metabolites. However, 11β-MNTG formation is highly variable and prevalent in human intestinal S9 fractions. A reaction phenotyping study of 11β-MNT using thirteen recombinant UDP-glucuronosyltransferase (UGT) enzymes confirmed the major role of UGT2B17 in 11β-MNTG formation. This was further supported by a strong correlation (R2 > 0.78) between 11β-MNTG and UGT2B17 abundance in human intestinal microsomes, human liver microsomes, and HH systems. These results suggest that 11β-MNT and its prodrugs are rapidly metabolized to 11β-MNTG by the highly polymorphic intestinal UGT2B17, which may explain the poor and variable bioavailability of the drug. Full article
(This article belongs to the Special Issue Advances in ADME for Drug Discovery)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-2
Back to TopTop