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Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats
Antimicrobial peptide (Piscidin-1) is an effective natural polypeptide, which has great influence and potential on porcine epidemic diarrhea virus (PEDV) and pseudorabies virus (PRV). As an alternative antibiotic substitute, Piscidin-1 was subjected for pharmacokinetics study with three administrati...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026642/ https://www.ncbi.nlm.nih.gov/pubmed/29988520 http://dx.doi.org/10.3389/fchem.2018.00244 |
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author | Lei, Zhixin Liu, Qianying Zhu, Qianqian Yang, Bing Khaliq, Haseeb Sun, Ao Qi, Yi Moku, Gopi Krishna Su, Yafan Wang, Jiawei Cao, Jiyue He, Qigai |
author_facet | Lei, Zhixin Liu, Qianying Zhu, Qianqian Yang, Bing Khaliq, Haseeb Sun, Ao Qi, Yi Moku, Gopi Krishna Su, Yafan Wang, Jiawei Cao, Jiyue He, Qigai |
author_sort | Lei, Zhixin |
collection | PubMed |
description | Antimicrobial peptide (Piscidin-1) is an effective natural polypeptide, which has great influence and potential on porcine epidemic diarrhea virus (PEDV) and pseudorabies virus (PRV). As an alternative antibiotic substitute, Piscidin-1 was subjected for pharmacokinetics study with three administration routes (i.v, i.m, and p.o) after a single dose of 2 mg/kg in rats and preliminary pharmacodynamics including antiviral activity in cell against PEDV and PRV. Based on 50 percent tissue culture infective dose (TCID(50)), there were about 2 and 10% virus survived ratios for Piscidin-1 against PRV and PEDV, respectively. The plaque test showed 1 and 2 μg/ml Piscidin-1 could eliminate 95% PRV and 85% PEDV, respectively. The main pharmacokinetics parameters of C(max), AUC(0−∞), Ke, t(1/2), T(max), MRT, and Cl(b) in plasma were not applicable value, 25.9 μg(*)h/ml, 0.041 h(−1), 16.97 h, not available value, 22.77 h, 0.067 L/h(*)kg after i.v administration, 2.37 μg/ml, 18.95 μg(*)h/ml, 0.029 h(−1), 23.50 h, 0.33 h, 30.12 h, 0.095 L/h(*)kg after i.m administration and 0.73 μg/ml, 9.63 μg(*)h/ml, 0.036 h(−1), 19.46 h, 0.50 h, 26.76 h, 0.171 L/h(*)kg after p.o administration. The bioavailability values after i.m and p.o administrations were calculated as 73.17 and 37.18%, respectively. The i.m administration was selected for pharmacokinetics study in ileum content against PEDV. The main pharmacokinetic parameters of C(max), AUC(0−∞), Ke, t(1/2), T(max), MRT, and Cl(b) in ileum content were 1.67 μg/ml, 78.40 μg(*)h/ml, 0.034 h(−1), 20.16 h, 8.12 h, 36.45 h, 0.026 L/h(*)kg. The C(max) values in plasma (2.37 μg/ml) and ileum content (1.67 μg/ml) were higher than the effective inhibitory concentration determined in the plaque test, and this indicates that Piscidin-1 might have effective inhibition effect against PRV and PEDV after administration of 2 mg/kg i.m. The results of this study represent the first investigations toward the pharmacokinetic characteristics of piscidin-1 in plasma upon three different administration routes, among which i.m. resulted in the highest bioavailability (73.17%). Furthermore, the pharmacokinetics study of ileum content indicated Piscidin-1 might have good effect against PEDV and could be regarded as an alternative antibiotic in clinical veterinary in the future study. |
format | Online Article Text |
id | pubmed-6026642 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60266422018-07-09 Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats Lei, Zhixin Liu, Qianying Zhu, Qianqian Yang, Bing Khaliq, Haseeb Sun, Ao Qi, Yi Moku, Gopi Krishna Su, Yafan Wang, Jiawei Cao, Jiyue He, Qigai Front Chem Chemistry Antimicrobial peptide (Piscidin-1) is an effective natural polypeptide, which has great influence and potential on porcine epidemic diarrhea virus (PEDV) and pseudorabies virus (PRV). As an alternative antibiotic substitute, Piscidin-1 was subjected for pharmacokinetics study with three administration routes (i.v, i.m, and p.o) after a single dose of 2 mg/kg in rats and preliminary pharmacodynamics including antiviral activity in cell against PEDV and PRV. Based on 50 percent tissue culture infective dose (TCID(50)), there were about 2 and 10% virus survived ratios for Piscidin-1 against PRV and PEDV, respectively. The plaque test showed 1 and 2 μg/ml Piscidin-1 could eliminate 95% PRV and 85% PEDV, respectively. The main pharmacokinetics parameters of C(max), AUC(0−∞), Ke, t(1/2), T(max), MRT, and Cl(b) in plasma were not applicable value, 25.9 μg(*)h/ml, 0.041 h(−1), 16.97 h, not available value, 22.77 h, 0.067 L/h(*)kg after i.v administration, 2.37 μg/ml, 18.95 μg(*)h/ml, 0.029 h(−1), 23.50 h, 0.33 h, 30.12 h, 0.095 L/h(*)kg after i.m administration and 0.73 μg/ml, 9.63 μg(*)h/ml, 0.036 h(−1), 19.46 h, 0.50 h, 26.76 h, 0.171 L/h(*)kg after p.o administration. The bioavailability values after i.m and p.o administrations were calculated as 73.17 and 37.18%, respectively. The i.m administration was selected for pharmacokinetics study in ileum content against PEDV. The main pharmacokinetic parameters of C(max), AUC(0−∞), Ke, t(1/2), T(max), MRT, and Cl(b) in ileum content were 1.67 μg/ml, 78.40 μg(*)h/ml, 0.034 h(−1), 20.16 h, 8.12 h, 36.45 h, 0.026 L/h(*)kg. The C(max) values in plasma (2.37 μg/ml) and ileum content (1.67 μg/ml) were higher than the effective inhibitory concentration determined in the plaque test, and this indicates that Piscidin-1 might have effective inhibition effect against PRV and PEDV after administration of 2 mg/kg i.m. The results of this study represent the first investigations toward the pharmacokinetic characteristics of piscidin-1 in plasma upon three different administration routes, among which i.m. resulted in the highest bioavailability (73.17%). Furthermore, the pharmacokinetics study of ileum content indicated Piscidin-1 might have good effect against PEDV and could be regarded as an alternative antibiotic in clinical veterinary in the future study. Frontiers Media S.A. 2018-06-25 /pmc/articles/PMC6026642/ /pubmed/29988520 http://dx.doi.org/10.3389/fchem.2018.00244 Text en Copyright © 2018 Lei, Liu, Zhu, Yang, Khaliq, Sun, Qi, Moku, Su, Wang, Cao and He. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Chemistry Lei, Zhixin Liu, Qianying Zhu, Qianqian Yang, Bing Khaliq, Haseeb Sun, Ao Qi, Yi Moku, Gopi Krishna Su, Yafan Wang, Jiawei Cao, Jiyue He, Qigai Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats |
title | Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats |
title_full | Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats |
title_fullStr | Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats |
title_full_unstemmed | Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats |
title_short | Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats |
title_sort | comparative pharmacokinetics and preliminary pharmacodynamics evaluation of piscidin 1 against prv and pedv in rats |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026642/ https://www.ncbi.nlm.nih.gov/pubmed/29988520 http://dx.doi.org/10.3389/fchem.2018.00244 |
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