Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats

Zhixin Lei; Qianying Liu; Qianqian Zhu; Bing Yang; Haseeb Khaliq; Ao Sun; Yi Qi; Gopi Krishna Moku; Yafan Su; Jiawei Wang; Jiyue Cao; Qigai He

doi:10.3389/fchem.2018.00244

Comparative Pharmacokinetics and Preliminary Pharmacodynamics Evaluation of Piscidin 1 Against PRV and PEDV in Rats

Front Chem. 2018 Jun 25:6:244. doi: 10.3389/fchem.2018.00244. eCollection 2018.

Authors

Zhixin Lei^{1

2

3

4}, Qianying Liu^{1

2

3}, Qianqian Zhu^{1

2}, Bing Yang^{1

2}, Haseeb Khaliq¹, Ao Sun^{1

2}, Yi Qi¹, Gopi Krishna Moku⁴, Yafan Su⁴, Jiawei Wang⁴, Jiyue Cao^{2

3}, Qigai He¹

Affiliations

¹ State Key Laboratory of Agriculture Microbiology, College of Veterinary Medicine, Huazhong Agriculture University, Wuhan, China.
² Department of Veterinary Pharmacology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
³ National Reference Laboratory of Veterinary Drug Residues and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agriculture University, Wuhan, China.
⁴ Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, United States.

Abstract

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 (TCID₅₀), 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.

Keywords: PEDV; Piscidin-1; bioavailability; ileum content; pharmacokinetics.