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...

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Autores principales:	Su He, Wenjia Zhao, Peibo Li, Wenqing Tu, Kui Hong, Duoduo Zhang, Tongke Zhang, Ganjun Yuan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	azalomycin F pharmacokinetics rat bioavailability macrolide antimicrobial agent Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/b95b235b8dea4f4db43e73a8c5525aed
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spelling	oai:doaj.org-article:b95b235b8dea4f4db43e73a8c5525aed2021-11-11T18:28:22ZPharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats10.3390/molecules262164641420-3049https://doaj.org/article/b95b235b8dea4f4db43e73a8c5525aed2021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6464https://doaj.org/toc/1420-3049As 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.Su HeWenjia ZhaoPeibo LiWenqing TuKui HongDuoduo ZhangTongke ZhangGanjun YuanMDPI AGarticleazalomycin Fpharmacokineticsratbioavailabilitymacrolideantimicrobial agentOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6464, p 6464 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	azalomycin F pharmacokinetics rat bioavailability macrolide antimicrobial agent Organic chemistry QD241-441
spellingShingle	azalomycin F pharmacokinetics rat bioavailability macrolide antimicrobial agent Organic chemistry QD241-441 Su He Wenjia Zhao Peibo Li Wenqing Tu Kui Hong Duoduo Zhang Tongke Zhang Ganjun Yuan Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats
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	article
author	Su He Wenjia Zhao Peibo Li Wenqing Tu Kui Hong Duoduo Zhang Tongke Zhang Ganjun Yuan
author_facet	Su He Wenjia Zhao Peibo Li Wenqing Tu Kui Hong Duoduo Zhang Tongke Zhang Ganjun Yuan
author_sort	Su He
title	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_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_sort	pharmacokinetics of azalomycin f, a natural macrolide produced by streptomycete strains, in rats
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b95b235b8dea4f4db43e73a8c5525aed
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Pharmacokinetics of Azalomycin F, a Natural Macrolide Produced by Streptomycete Strains, in Rats

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