Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.4
4.2
Journals
Molecules
Special Issues
Drug Metabolism and Pharmacokinetics: Current Trends and Future Perspectives
molecules-logo
Submit to Molecules Review for Molecules Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Drug Metabolism and Pharmacokinetics: Current Trends and Future Perspectives

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 12422

Special Issue Editors

Prof. Dr. Satomi Onoue

E-Mail Website
Guest Editor
Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
Interests: drug delivery system; biopharmaceutics; peptides; safety science
Dr. Dorota Danielak

E-Mail Website
Guest Editor
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego St., 60-781 Poznań, Poland
Interests: pharmacokinetics; pharmacogenetics; antiplatelet drugs; pharmacometrics; method validation
Dr. Katarzyna Kosicka-Noworzyń

E-Mail Website
Guest Editor
Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Collegium Maius, Fredry 10, 61-701 Poznań, Poland
Interests: pharmacokinetics; bioanalytical method validation; analysis of endogenous compounds; therapeutic monoclonal antibodies

Special Issue Information

Dear Colleagues,

Adequate information on systemic exposure to a drug is a critical factor in the development process. It is essential for newly designed drugs and finding the clinical proof for traditionally used remedies' efficacy. Besides, assessment of pharmacokinetics of the active pharmaceutical ingredients enables the prediction of the therapeutic success, from animal models to phase III clinical trials. Moreover, a detailed pharmacokinetic analysis often leads to discovering the causes of an inadequate response to the drug. For example, the drug exposure might be lower due to the insufficient activity of one of the enzymes in the metabolic pathway.

The cornerstone of pharmacokinetics is an accurate determination of the active moieties in collected samples. For this purpose, the researchers aim to develop the most precise and accurate analytical methods. Undeniably, the benchmark is mass spectrometry methods, which are deemed as the most sensitive. However, alternative approaches such as immunoenzymatic methods are also considered, mainly due to time and cost efficiency.

This Special Issue focuses on the development and application of bioanalytical methods for pharmacokinetic analysis. Submitted manuscripts should focus on one of the following aspects:

  • Highlighting the advantage of the novel method over currently used ones,
  • Comparison of bioanalytical approaches for determination of pharmaceutical ingredients in biological matrices,
  • Application of the method for establishing pharmacokinetics of a novel pharmaceutical ingredient or herbal extracts,
  • Application of the method for a better understanding of drug metabolism and disposition.

Prof. Dr. Satomi Onoue
Dr. Dorota Danielak
Dr. Katarzyna Kosicka-Noworzyń
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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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
  • bioanalytical methods
  • method validation
  • metabolism

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.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

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

Published Papers (4 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

14 pages, 1901 KiB  
Article
The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia
by Hawsar Othman Mohammed, Attila Almási, Szilárd Molnár and Pál Perjési
Molecules 2022, 27(13), 4000; https://doi.org/10.3390/molecules27134000 - 22 Jun 2022
Cited by 2 | Viewed by 1978
Abstract
Hyperglycemia is reported to be associated with oxidative stress. It can result in changes in the activities of drug-metabolizing enzymes and membrane-integrated transporters, which can modify the fate of drugs and other xenobiotics; furthermore, it can result in the formation of non-enzyme catalyzed [...] Read more.
Hyperglycemia is reported to be associated with oxidative stress. It can result in changes in the activities of drug-metabolizing enzymes and membrane-integrated transporters, which can modify the fate of drugs and other xenobiotics; furthermore, it can result in the formation of non-enzyme catalyzed oxidative metabolites. The present work aimed to investigate how experimental hyperglycemia affects the intestinal and biliary appearance of the oxidative and Phase II metabolites of ibuprofen in rats. In vivo studies were performed by luminal perfusion of 250 μM racemic ibuprofen solution in control and streptozotocin-treated (hyperglycemic) rats. Analysis of the collected intestinal perfusate and bile samples was performed by HPLC-UV and HPLC-MS. No oxidative metabolites could be detected in the perfusate samples. The biliary appearance of ibuprofen, 2-hydroxyibuprofen, ibuprofen glucuronide, hydroxylated ibuprofen glucuronide, and ibuprofen taurate was depressed in the hyperglycemic animals. However, no specific non-enzymatic (hydroxyl radical initiated) hydroxylation product could be detected. Instead, the depression of biliary excretion of ibuprofen and ibuprofen metabolites turned out to be the indicative marker of hyperglycemia. The observed changes impact the pharmacokinetics of drugs administered in hyperglycemic individuals. Full article
(This article belongs to the Special Issue Drug Metabolism and Pharmacokinetics: Current Trends and Future Perspectives)
►▼ Show Figures

Figure 1

17 pages, 695 KiB  
Article
Preclinical Pharmacokinetics and Acute Toxicity in Rats of 5-{[(2E)-3-Bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic Acid: A Novel 5-Aminosalicylic Acid Derivative with Potent Anti-Inflammatory Activity
by Mara Gutiérrez-Sánchez, Aurelio Romero-Castro, José Correa-Basurto, Martha Cecilia Rosales-Hernández, Itzia Irene Padilla-Martínez and Jessica Elena Mendieta-Wejebe
Molecules 2021, 26(22), 6801; https://doi.org/10.3390/molecules26226801 - 11 Nov 2021
Cited by 2 | Viewed by 2642
Abstract
Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (C1), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study [...] Read more.
Compound 5-{[(2E)-3-bromo-3-carboxyprop-2-enoyl]amino}-2-hydroxybenzoic acid (C1), a new 5-aminosalicylic acid (5-ASA) derivative, has proven to be an antioxidant in vitro and an anti-inflammatory agent in mice. The in vivo inhibition of myeloperoxidase was comparable to that of indomethacin. The aim of this study was to take another step in the preclinical evaluation of C1 by examining acute toxicity with the up-and-down OECD method and pharmacokinetic profiles by administration of the compound to Wistar rats through intravenous (i.v.), oral (p.o.), and intraperitoneal (i.p.) routes. According to the Globally Harmonized System, C1 belongs to categories 4 and 5 for the i.p. and p.o. routes, respectively. An RP-HPLC method for C1 quantification in plasma was successfully validated. Regarding the pharmacokinetic profile, the elimination half-life was approximately 0.9 h with a clearance of 24 mL/min after i.v. administration of C1 (50 mg/kg). After p.o. administration (50 mg/kg), the maximum plasma concentration was reached at 33 min, the oral bioavailability was about 77%, and the compound was amply distributed to all tissues evaluated. Therefore, C1 administered p.o. in rats is suitable for reaching the colon where it can exert its effect, suggesting an important advantage over 5-ASA and indomethacin in treating ulcerative colitis and Crohn’s disease. Full article
(This article belongs to the Special Issue Drug Metabolism and Pharmacokinetics: Current Trends and Future Perspectives)
►▼ Show Figures

Graphical abstract

10 pages, 1420 KiB  
Article
Utilization of Sodium Nitroprusside as an Intestinal Permeation Enhancer for Lipophilic Drug Absorption Improvement in the Rat Proximal Intestine
by Hisanao Kishimoto, Kaori Miyazaki, Hiroshi Tedzuka, Ryosuke Ozawa, Hanai Kobayashi, Yoshiyuki Shirasaka and Katsuhisa Inoue
Molecules 2021, 26(21), 6396; https://doi.org/10.3390/molecules26216396 - 22 Oct 2021
Cited by 2 | Viewed by 3227
Abstract
As advanced synthetic technology has enabled drug candidate development with complex structure, resulting in low solubility and membrane permeability, the strategies to improve poorly absorbed drug bioavailability have attracted the attention of pharmaceutical companies. It has been demonstrated that nitric oxide (NO), a [...] Read more.
As advanced synthetic technology has enabled drug candidate development with complex structure, resulting in low solubility and membrane permeability, the strategies to improve poorly absorbed drug bioavailability have attracted the attention of pharmaceutical companies. It has been demonstrated that nitric oxide (NO), a vital signaling molecule that plays an important role in various physiological systems, affects intestinal drug absorption. However, NO and its oxidants are directly toxic to the gastrointestinal tract, thereby limiting their potential clinical application as absorption enhancers. In this study, we show that sodium nitroprusside (SNP), an FDA-approved vasodilator, enhances the intestinal absorption of lipophilic drugs in the proximal parts of the small intestine in rats. The SNP pretreatment of the rat gastrointestinal sacs significantly increased griseofulvin and flurbiprofen permeation in the duodenum and jejunum but not in the ileum and colon. These SNP-related enhancement effects were attenuated by the co-pretreatment with dithiothreitol or c-PTIO, an NO scavenger. The permeation-enhancing effects were not observed in the case of antipyrine, theophylline, and propranolol in the duodenum and jejunum. Furthermore, the SNP treatment significantly increased acidic glycoprotein release from the mucosal layers specifically in the duodenum and jejunum but not in the ileum and colon. These results suggest that SNP increases lipophilic drug membrane permeability specifically in the proximal region of the small intestine through disruption of the mucosal layer. Full article
(This article belongs to the Special Issue Drug Metabolism and Pharmacokinetics: Current Trends and Future Perspectives)
►▼ Show Figures

Graphical abstract

14 pages, 774 KiB  
Article
Potential Assessment of UGT2B17 Inhibition by Salicylic Acid in Human Supersomes In Vitro
by Hassan Salhab, Declan P. Naughton and James Barker
Molecules 2021, 26(15), 4410; https://doi.org/10.3390/molecules26154410 - 21 Jul 2021
Cited by 3 | Viewed by 3203
Abstract
Glucuronidation is a Phase 2 metabolic pathway responsible for the metabolism and excretion of testosterone to a conjugate testosterone glucuronide. Bioavailability and the rate of anabolic steroid testosterone metabolism can be affected upon UGT glucuronidation enzyme alteration. However, there is a lack of [...] Read more.
Glucuronidation is a Phase 2 metabolic pathway responsible for the metabolism and excretion of testosterone to a conjugate testosterone glucuronide. Bioavailability and the rate of anabolic steroid testosterone metabolism can be affected upon UGT glucuronidation enzyme alteration. However, there is a lack of information about the in vitro potential assessment of UGT2B17 inhibition by salicylic acid. The purpose of this study is to investigate if UGT2B17 enzyme activity is inhibited by salicylic acid. A UGT2B17 assay was developed and validated by HPLC using a C18 reversed phase column (SUPELCO 25 cm × 4.6 mm, 5 μm) at 246 nm using a gradient elution mobile phase system: (A) phosphate buffer (0.01 M) at pH = 3.8, (B) HPLC grade acetonitrile and (C) HPLC grade methanol. The UGT2B17 metabolite (testosterone glucuronide) was quantified using human UGT2B17 supersomes by a validated HPLC method. The type of inhibition was determined by Lineweaver–Burk plots. These were constructed from the in vitro inhibition of salicylic acid at different concentration levels. The UGT2B17 assay showed good linearity (R2 > 0.99), acceptable recovery and accuracy (80–120%), good reproducibility and acceptable inter and intra-assay precision (<15%), low detection (6.42 and 2.76 μM) and quantitation limit values (19.46 and 8.38 μM) for testosterone and testosterone glucuronide respectively, according to ICH guidelines. Testosterone and testosterone glucuronide were found to be stable up to 72 h in normal laboratory conditions. Our investigational study showed that salicylic acid uncompetitively inhibited UGT2B17 enzyme activity. Thus, drugs that are substrates for the UGT2B17 enzyme have negligible potential effect of causing interaction with salicylic acid in humans. Full article
(This article belongs to the Special Issue Drug Metabolism and Pharmacokinetics: Current Trends and Future Perspectives)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop