Pneumatic dart delivery of tulathromycin in calves results in lower antimicrobial concentrations and increased biomarkers of stress and injection site inflammation compared with subcutaneous injection

• Published in: Journal of animal science 2018-07, Vol.96 (8), p.3089-3101
• Main Authors: Coetzee, Johann F, Kleinhenz, Michael D, Magstadt, Drew R, Cooper, Vickie L, Wulf, Larry W, Van Engen, Nicholas K, Smith, Joseph S, Rand, Nathan, KuKanich, Butch, Gorden, Patrick J
• Format: Article
• Language: English
• Subjects: Animal Health and Well Being; Animal Welfare; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antiinfectives and antibacterials; Aspartate aminotransferase; Biomarkers; Biomarkers - blood; Calves; Cattle; Cortisol; Creatine; Creatine kinase; Disaccharides - administration & dosage; Disaccharides - pharmacokinetics; Drug delivery; Drug Delivery Systems; Heterocyclic Compounds - administration & dosage; Heterocyclic Compounds - pharmacokinetics; Inflammation; Inflammation - etiology; Inflammation - veterinary; Injection; Injections; Injections - adverse effects; Injections - veterinary; Injections, Subcutaneous - veterinary; Male; Muscles; Neck; Pain; Pain perception; Pharmacokinetics; Pharmacology; Pneumatics; Random Allocation; Stress; Stress, Physiological; Stresses; Thermography; Weight reduction
• ISSN: 0021-8812; 1525-3163
• DOI: 10.1093/jas/sky222

Abstract Remote drug delivery (RDD) using pneumatic darts has become more prevalent in situations where cattle handling facilities are not available. The objective of this study was to compare the effect of pneumatic dart delivery and subcutaneous injection of tulathromycin on plasma pharmacokinetics and biomarkers of inflammation, stress, and muscle injury in calves. Twenty-three castrated-male Holstein calves, approximately 10 mo of age with an average weight of 378 ± 6.49 kg, were randomly assigned to 1 of 2 groups. Calves in the RDD group (n = 15) received 10 mL of tulathromycin (2.42 to 2.93 mg/kg) delivered into the left neck using a Type U 10.0 mL 1.9-cm 14 G Needle pneumatic dart administered with a breech loading projector. With the exception of 1 light weight calf that received 7 mL (2.53 mg/kg), calves in the injection group (INJ) (n = 8) also received 10 mL of tulathromycin (2.34 to 2.68 mg/kg) administered as a single subcutaneous injection in the left neck using a 14 G, 1.9-cm needle and a 12-mL syringe. Serum tulathromycin, cortisol, creatine kinase (CK), and aspartate aminotransferase (AST) concentrations were determined in combination with other biomarkers of inflammation including mechanical nociceptive threshold (MNT), infrared thermography (IRT), and swelling at the injection site over 432 h after administration. Pneumatic darts failed to deliver the required dose of tulathromycin in 4 of 15 calves evidenced by heavier dart weights post-administration (24 vs. 13.5 g). When these 4 calves were removed from the analysis, calves in the RDD group were found to have a smaller area under the tulathromycin concentration curve (AUC) (P = 0.005) and faster clearance (P = 0.025) compared with the INJ group. Furthermore, the RDD group recorded a greater difference in MNT between the treated and contralateral neck compared with the INJ group at 12 h (P = 0.016), 216 h (P = 0.024), and 288 h (P = 0.0494) after administration. Serum CK was elevated at 24 h (P = 0.03) and AST was greater at 24 h (P = 0.024) and 48 h (P = 0.037) after RDD. Serum cortisol concentrations were also greater at 0.5 h (P = 0.02) after RDD. These findings suggest that RDD is associated with reduced total body exposure to tulathromycin and increased acute stress, muscle damage, and pain at the injection site. Furthermore, the failure of darts to consistently deliver antimicrobial therapy has a negative impact on the welfare of sick animals treated with RDD technologies.