Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with Mannheimia hemolytica

• Published in: Journal of veterinary internal medicine 2025-01, Vol.39 (1), p.e17270
• Main Authors: Foster, Derek M, Halleran, Jennifer L, Jacob, Megan E, Hempstead, Stephanie, Borst, Luke B, Negrao Watanabe, Tatiane T, Enomoto, Hiroko, Papich, Mark G
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - therapeutic use; Cattle; Cattle Diseases - drug therapy; Disaccharides - pharmacokinetics; Disaccharides - therapeutic use; Fluoroquinolones - pharmacokinetics; Fluoroquinolones - therapeutic use; Heterocyclic Compounds - pharmacokinetics; Heterocyclic Compounds - therapeutic use; Macrolides; Male; Mannheimia haemolytica - drug effects; Pasteurella Infections - drug therapy; Pasteurella Infections - veterinary; STANDARD ARTICLE; Thiamphenicol - analogs & derivatives; Thiamphenicol - pharmacokinetics; Thiamphenicol - therapeutic use
• ISSN: 0891-6640; 1939-1676; 1939-1676
• DOI: 10.1111/jvim.17270

Bovine respiratory disease (BRD) is an economically important disease in the beef industry, and a major driver of therapeutic antibiotic use. Pharmacokinetic data of these drugs is relatively limited in diseased animals. To determine the concentrations of pradofloxacin, florfenicol, and tulathromycin in the airways, plasma, and interstitial fluid (ISF) of steers with a clinically relevant model of bacterial respiratory disease. Twenty-four Holstein and Holstein/Jersey cross steers ranging in age from 6 to 15 months. A randomized, blinded clinical trial was performed. After transport stress, steers were inoculated with Mannheimia hemolytica to induce BRD. Upon onset of clinical disease, steers were treated with pradofloxacin, florfenicol or tulathromycin. Blood, ISF, and pulmonary epithelial lining fluid (PELF) samples were obtained for drug concentration determination. Clinical exams and thoracic ultrasound examinations were conducted daily. Animals were euthanized at the end of the study period to assess lung lesions. Pradofloxacin C in PELF was 0.81 μg/mL (CV = 49.02%) and penetration into the PELF was 203.58% (72%). Florfenicol C in PELF was 2.94 μg/mL (42.1%) and penetration was 230.08% (78.82%). Tulathromycin PELF C was 0.9 μg/mL (45.03%) and PELF penetration was 518.97% (56.59%). There are differences in penetration of the drugs into the ISF and PELF compared to one another and previous data from healthy steers demonstrating the effect of disease on the PK of these drugs.