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Marine Drugs
Special Issues
Pharmacokinetic Research of Marine Drugs
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Pharmacokinetic Research of Marine Drugs

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 25838

Special Issue Editor

Prof. Dr. Alexander N. Shikov

E-Mail Website
Guest Editor
Department of Technology of Pharmaceutical Formulations, Saint-Petersburg State Chemical Pharmaceutical University, Saint-Petersburg, Russia
Interests: natural products; sea urchins; algae; chemistry; pharmacology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Marine species have become increasingly popular sources of new high-activity molecules. Papers about the isolation and identification of such compounds have increased gradually. However, just a few of compounds are used in clinical practice. It is essential for the development process of drugs to analyze active molecules through pharmacokinetics (PK). The understanding of absorption, distribution, metabolism, and excretion (ADME) is the basis for theoretical drug design. Reliable analytical methods are required for understanding pharmacokinetics and metabolism. All routine techniques, alternative analytical methods, such as ELISA, and other indirect assays are necessary for studies on PK and ADME. This Special Issue is focused on the situation and frontiers of studies on the pharmacokinetics and metabolism of marine molecular drugs. Original research papers and all aspects of pharmacokinetics and metabolism are welcomed to highlight the potential of compounds isolated from marine species for the further development of marine drugs.

Prof. Dr. Alexander N. Shikov
Guest Editor

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. Marine Drugs 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

  • Marine species
  • Pharmacokinetic
  • Absorption, Distribution, Metabolism, Excretion
  • Analytical techniques
  • In vivo studies

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Published Papers (5 papers)

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Research

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9 pages, 717 KiB  
Article
The Pharmacokinetics of Fucoidan after Topical Application to Rats
by Olga N. Pozharitskaya, Alexander N. Shikov, Ekaterina D. Obluchinskaya and Heikki Vuorela
Mar. Drugs 2019, 17(12), 687; https://doi.org/10.3390/md17120687 - 6 Dec 2019
Cited by 54 | Viewed by 6568
Abstract
Fucoidan, a fucose-rich polysaccharide from brown algae, has been used for transdermal formulations targeting inflammatory skin conditions, for the treatment of thrombosis, vascular permeability diseases, subcutaneous wounds, and burns. However, the pharmacokinetics of fucoidan after topical application has not been described. In this [...] Read more.
Fucoidan, a fucose-rich polysaccharide from brown algae, has been used for transdermal formulations targeting inflammatory skin conditions, for the treatment of thrombosis, vascular permeability diseases, subcutaneous wounds, and burns. However, the pharmacokinetics of fucoidan after topical application has not been described. In this study, an ointment (OF) containing 15% fucoidan was topically applied to rats at the doses of 50–150 mg/g. The anti-Xa activity was selected as the biomarker, and the amidolytic assay method was validated and applied for pharmacokinetic studies of fucoidan. Fucoidan in OF penetrated the skin and distributed into the skin, striated muscle, and plasma with AUC0–48 = 0.94 μg·h/g, 2.22 μg·h/g, and 1.92 µg·h/mL, respectively. The longest half-life for fucoidan was observed in plasma, then in striated muscle and skin. It was found that the pharmacokinetics of fucoidan after topical OF application was linear, in the range of 50–150 mg/kg. No accumulation of fucoidan in plasma was observed after repeated topical applications of 100 mg/kg during five days. Our results support the rationality of topical application of formulations with fucoidan. Full article
(This article belongs to the Special Issue Pharmacokinetic Research of Marine Drugs)
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18 pages, 4714 KiB  
Article
Toxicity, Pharmacokinetics, and Gut Microbiome of Oral Administration of Sesterterpene MHO7 Derived from a Marine Fungus
by Wei Tian, Liang Yang, Di Wu, Zixin Deng and Kui Hong
Mar. Drugs 2019, 17(12), 667; https://doi.org/10.3390/md17120667 - 26 Nov 2019
Cited by 5 | Viewed by 3319
Abstract
Sesterterpene MHO7 derived from mangrove fungus is a novel estrogen receptor degrader for the treatment of breast cancer. To explore its safety and pharmacokinetics in vivo, Log P/D values, stability in simulated gastric/intestinal (SGF/SIF), toxicity, and pharmacokinetics studies were carried mainly by liquid [...] Read more.
Sesterterpene MHO7 derived from mangrove fungus is a novel estrogen receptor degrader for the treatment of breast cancer. To explore its safety and pharmacokinetics in vivo, Log P/D values, stability in simulated gastric/intestinal (SGF/SIF), toxicity, and pharmacokinetics studies were carried mainly by liquid chromatography technique coupled with tandem mass spectrometry (LC–MS/MS) method in mice, and the effect of MHO7 on mice gut microbiota at different time points was revealed by 16S rRNA sequencing. Log P/D values ranged 0.93–2.48, and the compound in SGF and SIF is stable under the concentration of 5 mM·L−1. The maximum tolerance dose (MTD) of oral administration in mice was 2400 mg·kg−1. The main pharmacokinetics parameters were as following: Cmax of 1.38 μg·mL−1, Tmax of 8 h, a half-life (t1/2) of 6.97 h, an apparent volume of mean residual time (MRT) of 8.76 h, and an area under the curve (AUC) of 10.50 h·μg·mL−1. MHO7 displayed a wide tissue distribution in mice, with most of the compound in liver (3.01 ± 1.53 μg·g−1) at 1 h, then in fat (5.20 ± 3.47 μg·g−1) at 4 h, and followed by reproductive organs with the concentrations of 23.90 ± 11.33 μg·g−1,13.69 ± 10.29 μg·g−1, 1.46 ± 1.23 μg·g−1, and 0.36 ± 0.46 μg·g−1 at 8, 12, 20 and 30 h, respectively. The most influenced genera of gut microbiome belonged to phylum Firmicutes (21 of 28), among which 18 genera originated from the order Clostridiales, class Clostridia, and families of Ruminococcaceae (11 of 18) and Lachnospiraceae (4 of 18). These results provide that MHO7 is suitable for oral administration in the treatment of breast cancer with the target organs of reproductive organs and regulation on Ruminococcaceae and Lachnospiraceae. Full article
(This article belongs to the Special Issue Pharmacokinetic Research of Marine Drugs)
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14 pages, 2807 KiB  
Article
Pharmacokinetic Study of Bioactive Glycopeptide from Strongylocentrotus droebachiensis After Intranasal Administration to Rats Using Biomarker Approach
by Alexander N. Shikov, Olga N. Pozharitskaya, Natalia M. Faustova, Vera M. Kosman, Valery G. Makarov, Ebrahim Razzazi-Fazeli and Johannes Novak
Mar. Drugs 2019, 17(10), 577; https://doi.org/10.3390/md17100577 - 11 Oct 2019
Cited by 9 | Viewed by 3059
Abstract
A glycopeptide fraction (GPF) from internal organs of green sea urchins (Strongylocentrotus droebachiensis Müller, Strongylocentrotidae) has been reported to be an effective bronchitis treatment. In this study, we evaluated the pharmacokinetic and tissue distribution of GPF, following single and repeated intranasal (i/n) [...] Read more.
A glycopeptide fraction (GPF) from internal organs of green sea urchins (Strongylocentrotus droebachiensis Müller, Strongylocentrotidae) has been reported to be an effective bronchitis treatment. In this study, we evaluated the pharmacokinetic and tissue distribution of GPF, following single and repeated intranasal (i/n) administration over the course of seven days in rats. The method measuring lactate dehydrogenase as biomarker was used to analyse the plasma and tissue concentrations of GPF. GPF appears in the plasma 15 min after single i/n administration (100 µg/kg) and reaches its maximum at 45 min. The area under the curve (AUC)0–24 and Cmax were similar using both i/n and intravenous administration, while mean residence time (MRT) and T1/2 after i/n administration were significantly higher compared with intravenous (i/v) administration. The absolute bioavailability of GPF after i/n administration was 89%. The values of tissue availability (ft) provided evidence about the highest concentration of GPF in the nose mucosa (ft = 34.9), followed by spleen (ft = 4.1), adrenal glands (ft = 3.8), striated muscle (ft = 1.8), kidneys (ft = 0.5), and liver (ft = 0.3). After repeated dose administration, GPF exhibited significantly higher AUC0–24 and MRT, indicating its accumulation in the plasma. Full article
(This article belongs to the Special Issue Pharmacokinetic Research of Marine Drugs)
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11 pages, 5059 KiB  
Article
Stereo-Selective Pharmacokinetics of Ilimaquinone Epimers Extracted from a Marine Sponge in Rats
by Heebin Son, Keumhan Noh, InWha Park, MinKyun Na, Sangtaek Oh, Beom Soo Shin and Wonku Kang
Mar. Drugs 2019, 17(3), 171; https://doi.org/10.3390/md17030171 - 17 Mar 2019
Cited by 5 | Viewed by 3182
Abstract
An ilimquinone (IQ) mixture isolated from Hippiospongia metachromia, consisting of IQ and epi-ilimaquinone (epi-IQ), exerts anti-HIV, anti-microbial, anti-inflammatory, and anti-cancer effects. An HPLC-MS/MS method was developed for simultaneous determination of the two epimers in rat plasma, separating them using a biphenyl column. [...] Read more.
An ilimquinone (IQ) mixture isolated from Hippiospongia metachromia, consisting of IQ and epi-ilimaquinone (epi-IQ), exerts anti-HIV, anti-microbial, anti-inflammatory, and anti-cancer effects. An HPLC-MS/MS method was developed for simultaneous determination of the two epimers in rat plasma, separating them using a biphenyl column. Ascorbic acid is added during the sample preparation to ensure the stability of both isomers. The plasma concentrations of the isomers were monitored following intravenous and oral administration of the IQ mixture in rats as well as the individual epimers that were separately orally administered. Compare to IQ, epi-IQ was much more stable in rat plasma, likely due to its configurations of decalin. Both substances decayed in more than bi-exponential pattern, with an elimination rate constant of 1.2 h−1 for IQ and 1.7 h−1 for epi-IQ. The epi-IQ was distributed more widely than IQ by about two-fold. Consequently, the clearance of epi-IQ was greater than that of IQ by about three-fold. The oral absolute bioavailability for IQ was 38%, and, that for epi-IQ, was 13%. Although the systemic exposure of IQ was greater than that of epi-IQ by ~8.7-fold, the clearance of each isomer was similar when administered either orally or intravenously, when normalized for bioavailability. The stereo-specific behavior of the isomers appears to originate from differences in both their tissue distribution and gastrointestinal permeability. Full article
(This article belongs to the Special Issue Pharmacokinetic Research of Marine Drugs)
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Review

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35 pages, 2182 KiB  
Review
Pharmacokinetics of Marine-Derived Drugs
by Alexander N. Shikov, Elena V. Flisyuk, Ekaterina D. Obluchinskaya and Olga N. Pozharitskaya
Mar. Drugs 2020, 18(11), 557; https://doi.org/10.3390/md18110557 - 9 Nov 2020
Cited by 56 | Viewed by 8941
Abstract
Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has attracted increasing interest in recent decades due to its effective and potential contribution to the selection of rational [...] Read more.
Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has attracted increasing interest in recent decades due to its effective and potential contribution to the selection of rational dosage recommendations and the optimal use of the therapeutic arsenal. In general, pharmacokinetics studies how drugs change after administration via the processes of absorption, distribution, metabolism, and excretion (ADME). This review provides a summary of the pharmacokinetics studies of marine-derived active compounds, with a particular focus on their ADME. The pharmacokinetics of compounds derived from algae, crustaceans, sea cucumber, fungus, sea urchins, sponges, mollusks, tunicate, and bryozoan is discussed, and the pharmacokinetics data in human experiments are analyzed. In-depth characterization using pharmacokinetics is useful for obtaining information for understanding the molecular basis of pharmacological activity, for correct doses and treatment schemes selection, and for more effective drug application. Thus, an increase in pharmacokinetic research on marine-derived compounds is expected in the near future. Full article
(This article belongs to the Special Issue Pharmacokinetic Research of Marine Drugs)
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