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Pharmaceutics
Special Issues
Pharmacokinetic Properties in Drug Development
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Pharmacokinetic Properties in Drug Development

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

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 7679

Special Issue Editors

Dr. Luciana Scotti

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Guest Editor
Cheminformatics Laboratory-Postgraduate Program in Natural Products and Synthetic Bioactive, Federal University of Paraíba-Campus I, 58051-970 João Pessoa-PB, Brazil
Interests: molecular modelling; cheminformatics; natural products
Dr. Anne Rodallec

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Guest Editor
SMARTc, CRCM, Inserm UMR1068, CNRS UMR7258, Aix Marseille Université U105, Institut Paoli Calmettes, Marseille, France
Interests: nanomedicine; pharmacokinetics; oncology; drug delivery; oncopharmacology; PK/PD modeling; PBPK

Special Issue Information

Dear Colleagues,

In pharmaceutical research, pharmacokinetic properties (absorption, distribution, metabolism, and excretion (ADME)) have been recognized as one of the major factors for the decline in the success of new drugs. In the last 30 years, the development of new bioassay techniques, biotechnology methods, bioguided phytochemical studies, automated high throughput screening, and high-performance analytical methods has introduced new concepts and possibilities in drug discovery. In silico methods, spectroscopic techniques, and organic chemistry studies have been able to elucidate quickly complex molecular structures, and there has been a huge drive to perform well much earlier in the process of ADME elucidations and, more importantly, before the drug candidate is selected (in the lead-optimization phase), so that only compounds with high potency and good pharmacokinetic properties are chosen for development.

This issue will include studies on drug absorption evaluations; metabolism or biotransformation of toxicants; oxidation, reduction, and hydrolysis mechanism studies; theoretic prediction approaches; and metabolic pathway elucidations. Thus, scientific studies that seek to interpret and improve the ADMET properties of drug candidates are welcome.

Dr. Luciana Scotti
Dr. Anne Rodallec
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

  • ADMET
  • in silico
  • drug absorption evaluations
  • metabolism or biotransformation of toxicants
  • oxidation, reduction, and hydrolysis mechanism studies
  • pharmacokinetic properties

Published Papers (3 papers)

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Research

17 pages, 3539 KiB  
Article
Toxicokinetics of β-Amanitin in Mice and In Vitro Drug–Drug Interaction Potential
by Young Yoon Bang, Im-Sook Song, Min Seo Lee, Chang Ho Lim, Yong-Yeon Cho, Joo Young Lee, Han Chang Kang and Hye Suk Lee
Pharmaceutics 2022, 14(4), 774; https://doi.org/10.3390/pharmaceutics14040774 - 1 Apr 2022
Cited by 9 | Viewed by 2194
Abstract
The toxicokinetics of β-amanitin, a toxic bicyclic octapeptide present abundantly in Amanitaceae mushrooms, was evaluated in mice after intravenous (iv) and oral administration. The area under plasma concentration curves (AUC) following iv injection increased in proportion to doses of 0.2, 0.4, and 0.8 [...] Read more.
The toxicokinetics of β-amanitin, a toxic bicyclic octapeptide present abundantly in Amanitaceae mushrooms, was evaluated in mice after intravenous (iv) and oral administration. The area under plasma concentration curves (AUC) following iv injection increased in proportion to doses of 0.2, 0.4, and 0.8 mg/kg. β-amanitin disappeared rapidly from plasma with a half-life of 18.3–33.6 min, and 52.3% of the iv dose was recovered as a parent form. After oral administration, the AUC again increased in proportion with doses of 2, 5, and 10 mg/kg. Absolute bioavailability was 7.3–9.4%, which resulted in 72.4% of fecal recovery from orally administered β-amanitin. Tissue-to-plasma AUC ratios of orally administered β-amanitin were the highest in the intestine and stomach. It also readily distributed to kidney > spleen > lung > liver ≈ heart. Distribution to intestines, kidneys, and the liver is in agreement with previously reported target organs after acute amatoxin poisoning. In addition, β-amanitin weakly or negligibly inhibited major cytochrome P450 and 5′-diphospho-glucuronosyltransferase activities in human liver microsomes and suppressed drug transport functions in mammalian cells that overexpress transporters, suggesting the remote drug interaction potentials caused by β-amanitin exposure. Full article
(This article belongs to the Special Issue Pharmacokinetic Properties in Drug Development)
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16 pages, 5220 KiB  
Article
Design of Oral Sustained-Release Pellets by Modeling and Simulation Approach to Improve Compliance for Repurposing Sobrerol
by Chu-Hsun Lu, Yu-Feng Huang and I-Ming Chu
Pharmaceutics 2022, 14(1), 167; https://doi.org/10.3390/pharmaceutics14010167 - 11 Jan 2022
Cited by 1 | Viewed by 1753
Abstract
Sobrerol, an oral mucolytic agent, in a recent study showed promise for treating multiple sclerosis. A human equivalent dose of 486 mg of sobrerol administered thrice daily (i.e., 1459 mg of daily dose) demonstrated the highest therapeutic efficacy for repurposing use, which also [...] Read more.
Sobrerol, an oral mucolytic agent, in a recent study showed promise for treating multiple sclerosis. A human equivalent dose of 486 mg of sobrerol administered thrice daily (i.e., 1459 mg of daily dose) demonstrated the highest therapeutic efficacy for repurposing use, which also points out the poor compliance of administration. In this study, oral sustained-release pellets of sobrerol were successfully developed with evaluated manufacturing conditions and drug release kinetics. For design of the target drug product, we used a modeling and simulation approach to establish a predictive model of oral pharmacokinetic profile, by exploring the characteristics and correlations corresponding to the pharmacokinetics and pharmacodynamics of sobrerol, such as absorption lag time (0.18 h), time-scaling in vitro–in vivo correlation (tin-vitro = 0.494 tin-vivo − 0.0904), gastrointestinal transit time (8 h), minimum effective concentration (1.61 μg/mL), and duration of action (12.8 h). Results showed that the frequency of administration and the daily dose remarkably reduced by 33.3% (i.e., from thrice to twice daily) and 22.8%, respectively, which indicates that this prototype approach can be adopted for rapidly developing a modified-release dosage form of sobrerol, with improvement of compliance of administration and therapeutic efficacy. Full article
(This article belongs to the Special Issue Pharmacokinetic Properties in Drug Development)
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13 pages, 1953 KiB  
Article
Population Pharmacokinetics and Pharmacodynamic Target Attainment of Isavuconazole against Aspergillus fumigatus and Aspergillus flavus in Adult Patients with Invasive Fungal Diseases: Should Therapeutic Drug Monitoring for Isavuconazole Be Considered as Mandatory as for the Other Mold-Active Azoles?
by Pier Giorgio Cojutti, Alessia Carnelutti, Davide Lazzarotto, Emanuela Sozio, Anna Candoni, Renato Fanin, Carlo Tascini and Federico Pea
Pharmaceutics 2021, 13(12), 2099; https://doi.org/10.3390/pharmaceutics13122099 - 6 Dec 2021
Cited by 13 | Viewed by 2781
Abstract
Isavuconazole is a newer broad-spectrum triazole approved for the treatment of invasive fungal disease. The objective of this study was to conduct a population pharmacokinetic and pharmacodynamic analysis of isavuconazole in a retrospective cohort of hospitalized patients. A nonlinear mixed-effect approach with Monte [...] Read more.
Isavuconazole is a newer broad-spectrum triazole approved for the treatment of invasive fungal disease. The objective of this study was to conduct a population pharmacokinetic and pharmacodynamic analysis of isavuconazole in a retrospective cohort of hospitalized patients. A nonlinear mixed-effect approach with Monte Carlo simulations was conducted to assess the probability of target attainment (PTA) of an area under the concentration–time curve (AUC24 h)/minimum inhibitory concentration (MIC) ratio of 33.4 (defined as efficacy threshold against A. fumigatus and A. flavus) associated with a maintenance dose (MD) of 100, 200 and 300 mg daily after loading. The cumulative fraction of response (CFR) against the EUCAST MIC distributions of A. fumigatus and A. flavus was calculated as well. The proportion of trough concentrations (Ctrough) exceeding a defined threshold of toxicity (>5.13 mg/L) was estimated. A total of 50 patients, with a median age of 61.5 years, provided 199 plasma isavuconazole concentrations. Invasive pulmonary aspergillosis was the prevalent type of infection and accounted for 80% (40/50) of cases. No clinical covariates were retained by the model. With the standard MD of 200 mg daily, CFRs were always ≥90% during the first two months of treatment. The risk of Ctrough < 1.0 mg/L was around 1%, and that of Ctrough > 5.13 mg/L was 27.7 and 39.2% at 28 and 60 days, respectively, due to isavuconazole accumulation over time. Our findings suggest that TDM for isavuconazole should not be considered as mandatory as for the other mold-active azoles voriconazole and posaconazole. Full article
(This article belongs to the Special Issue Pharmacokinetic Properties in Drug Development)
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