1. WBC Abstract Submission
Anti-Microbial Resistance
WBC2016-228
Pharmacokinetics Of A Novel Antimicrobial Peptide In A Ruminant Model
Patrick Pithua* 1, B Angle 2, M F. Callahan2, K A. Gruber 2, J R. Middleton 1, B J. Johnson 1
1Veterinary Medicine and Surgery , University of Missouri-Columbia, 2Tensive Controls, Inc., Columbia, United States
Presentation Preference: Poster Presentation
Objectives: Multi-drug resistance has emerged as a significant challenge to public and veterinary medicine. Use of
antibiotics in food animal production is considered a driver of such resistance. Antimicrobial peptides (AMPs) based on
innate immune system cationic aromatic peptides could provide an effective alternative to traditional antibiotic use in food
animal production. The aim of this pilot study was to determine the pharmacokinetic properties of the antimicrobial
peptide TCMCB07 (hereafter B07) following oral, intramuscular and subcutaneous administration in preparation to
assess any clinical effects in healthy post weaned dairy calves.
Materials and Methods: This study was designed to advance AMP alternatives to antibiotic use due to the failure to
develop new antibiotics to combat multi-drug resistant organisms. The goal was to understand the pharmacodynamics of
antimicrobial peptides in vivo, to prepare for experiments examining their antibacterial action in food animals, particularly
ruminants. B07 was administered to 8 week old Holstein bull calves by oral, subcutaneous (SC), or intramuscular (IM)
administration. Blood sampling proceeded for 24 hours after administration. After the initial sampling period, intravenous
(IV) doses were given to three animals that received either SC or IM doses, and animals were sampled for another 24
hours. Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) was used to measure B07 concentrations
in bovine serum samples.
Results: The SC administration of 300 mg of B07 resulted in a 30 min peak of 1.68 ug/ml in blood, while the same dose
given IM resulted in a peak of 1.18 ug/ml at 15 min. The SC and IM doses had similar pharmacokinetic curves. A dose of
300 mg of B07 given orally resulted in a peak blood level of 0.11 ug/ml at 24 hours. The low recovery of B07 after oral
administration is likely due to extensive degradation of the peptide in the rumen. Two doses, 60 mg and 30 mg, given
intravenously resulted peak levels 1 min post administration of 8.96 ug/ml and 1.55 ug/ml, respectively.
Conclusions: The absorption of B07 in circulation was optimized following parenteral administration either
subcutaneously or intramuscularly. Experiment to determine the distribution of B07 in respiratory tissue is currently
underway in anticipation of its potential use for treating bovine respiratory disease.
Disclosure of Interest: None Declared