Cargando…

Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats

As antimicrobial resistance has been increasing, new antimicrobial agents are desperately needed. Azalomycin F, a natural polyhydroxy macrolide, presents remarkable antimicrobial activities. To investigate its pharmacokinetic characteristics in rats, the concentrations of azalomycin F contained in b...

Descripción completa

Detalles Bibliográficos
Autores principales: He, Su, Zhao, Wenjia, Li, Peibo, Tu, Wenqing, Hong, Kui, Zhang, Duoduo, Zhang, Tongke, Yuan, Ganjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588360/
https://www.ncbi.nlm.nih.gov/pubmed/34770873
http://dx.doi.org/10.3390/molecules26216464
_version_ 1784598436854628352
author He, Su
Zhao, Wenjia
Li, Peibo
Tu, Wenqing
Hong, Kui
Zhang, Duoduo
Zhang, Tongke
Yuan, Ganjun
author_facet He, Su
Zhao, Wenjia
Li, Peibo
Tu, Wenqing
Hong, Kui
Zhang, Duoduo
Zhang, Tongke
Yuan, Ganjun
author_sort He, Su
collection PubMed
description As antimicrobial resistance has been increasing, new antimicrobial agents are desperately needed. Azalomycin F, a natural polyhydroxy macrolide, presents remarkable antimicrobial activities. To investigate its pharmacokinetic characteristics in rats, the concentrations of azalomycin F contained in biological samples, in vitro, were determined using a validated high-performance liquid chromatography–ultraviolet (HPLC-UV) method, and, in vivo, samples were assayed by an ultra-high performance liquid chromatography–tandem mass spectrometric (UPLC–MS/MS) method. Based on these methods, the pharmacokinetics of azalomycin F were first investigated. Its plasma concentration-time courses and pharmacokinetic parameters in rats were obtained by a non-compartment model for oral (26.4 mg/kg) and intravenous (2.2 mg/kg) administrations. The results indicate that the oral absolute bioavailability of azalomycin F is very low (2.39 ± 1.28%). From combinational analyses of these pharmacokinetic parameters, and of the results of the in-vitro absorption and metabolism experiments, we conclude that azalomycin F is absorbed relatively slowly and with difficulty by the intestinal tract, and subsequently can be rapidly distributed into the tissues and/or intracellular f of rats. Azalomycin F is stable in plasma, whole blood, and the liver, and presents plasma protein binding ratios of more than 90%. Moreover, one of the major elimination routes of azalomycin F is its excretion through bile and feces. Together, the above indicate that azalomycin F is suitable for administration by intravenous injection when used for systemic diseases, while, by oral administration, it can be used in the treatment of diseases of the gastrointestinal tract.
format Online
Article
Text
id pubmed-8588360
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85883602021-11-13 Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats He, Su Zhao, Wenjia Li, Peibo Tu, Wenqing Hong, Kui Zhang, Duoduo Zhang, Tongke Yuan, Ganjun Molecules Article As antimicrobial resistance has been increasing, new antimicrobial agents are desperately needed. Azalomycin F, a natural polyhydroxy macrolide, presents remarkable antimicrobial activities. To investigate its pharmacokinetic characteristics in rats, the concentrations of azalomycin F contained in biological samples, in vitro, were determined using a validated high-performance liquid chromatography–ultraviolet (HPLC-UV) method, and, in vivo, samples were assayed by an ultra-high performance liquid chromatography–tandem mass spectrometric (UPLC–MS/MS) method. Based on these methods, the pharmacokinetics of azalomycin F were first investigated. Its plasma concentration-time courses and pharmacokinetic parameters in rats were obtained by a non-compartment model for oral (26.4 mg/kg) and intravenous (2.2 mg/kg) administrations. The results indicate that the oral absolute bioavailability of azalomycin F is very low (2.39 ± 1.28%). From combinational analyses of these pharmacokinetic parameters, and of the results of the in-vitro absorption and metabolism experiments, we conclude that azalomycin F is absorbed relatively slowly and with difficulty by the intestinal tract, and subsequently can be rapidly distributed into the tissues and/or intracellular f of rats. Azalomycin F is stable in plasma, whole blood, and the liver, and presents plasma protein binding ratios of more than 90%. Moreover, one of the major elimination routes of azalomycin F is its excretion through bile and feces. Together, the above indicate that azalomycin F is suitable for administration by intravenous injection when used for systemic diseases, while, by oral administration, it can be used in the treatment of diseases of the gastrointestinal tract. MDPI 2021-10-26 /pmc/articles/PMC8588360/ /pubmed/34770873 http://dx.doi.org/10.3390/molecules26216464 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
He, Su
Zhao, Wenjia
Li, Peibo
Tu, Wenqing
Hong, Kui
Zhang, Duoduo
Zhang, Tongke
Yuan, Ganjun
Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats
title Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats
title_full Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats
title_fullStr Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats
title_full_unstemmed Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats
title_short Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats
title_sort pharmacokinetics of azalomycin f, a natural macrolide produced by streptomycete strains, in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588360/
https://www.ncbi.nlm.nih.gov/pubmed/34770873
http://dx.doi.org/10.3390/molecules26216464
work_keys_str_mv AT hesu pharmacokineticsofazalomycinfanaturalmacrolideproducedbystreptomycetestrainsinrats
AT zhaowenjia pharmacokineticsofazalomycinfanaturalmacrolideproducedbystreptomycetestrainsinrats
AT lipeibo pharmacokineticsofazalomycinfanaturalmacrolideproducedbystreptomycetestrainsinrats
AT tuwenqing pharmacokineticsofazalomycinfanaturalmacrolideproducedbystreptomycetestrainsinrats
AT hongkui pharmacokineticsofazalomycinfanaturalmacrolideproducedbystreptomycetestrainsinrats
AT zhangduoduo pharmacokineticsofazalomycinfanaturalmacrolideproducedbystreptomycetestrainsinrats
AT zhangtongke pharmacokineticsofazalomycinfanaturalmacrolideproducedbystreptomycetestrainsinrats
AT yuanganjun pharmacokineticsofazalomycinfanaturalmacrolideproducedbystreptomycetestrainsinrats