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 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), 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, AUC, Ke, t, T, MRT, and Cl in plasma were not applicable value, 25.9 μh/ml, 0.041 h, 16.97 h, not available value, 22.77 h, 0.067 L/hkg after i.v administration, 2.37 μg/ml, 18.95 μh/ml, 0.029 h, 23.50 h, 0.33 h, 30.12 h, 0.095 L/hkg after i.m administration and 0.73 μg/ml, 9.63 μh/ml, 0.036 h, 19.46 h, 0.50 h, 26.76 h, 0.171 L/hkg 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, AUC, Ke, t, T, MRT, and Cl in ileum content were 1.67 μg/ml, 78.40 μh/ml, 0.034 h, 20.16 h, 8.12 h, 36.45 h, 0.026 L/hkg. The C 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.