Pharmacokinetics of florfenicol in healthy pigs after its intramuscular administration

GORTARI CASTILLO, LIHUEL; MARCHETTI, LAURA; BULDAIN, DANIEL; JULCA LOZANO, KAREN; ALIVERTI, FLORENCIA; BUCHAMER, ANDREA; MESTORINO, NORA

Conferencia; Tenth International Conference on Antimicrobial Agents in Veterinary Medicine (AAVM); 2020

Antimicrobial Agents in Veterinary Medicine (AAVM)

Florfenicol (FF) is a broad spectrum antibacterial agent and has potential to become a valuable antibiotic to treat pig infectious diseases. We evaluated the pharmacokinetic profile of FF after its intramuscular administration in pigs. Six healthy male pigs with body weight between 10 to 12 kg were housed as a group on straw bedding with water and food ad libitum, with a day/night cycle of 12 hours. FF 30% injectable solution at dose rate of 20 mg/kg bodyweight was administered intramuscularly in the neck, using an 18G 38 mm needle. Blood samples were obtained from jugular vein using heparinized vacuum tubes before drug administration and at 5, 1, 2, 4, 8, 12, 24 and 48 h after treatment. FF was determined by HPLC-UV with liquid/liquid extraction. Pharmacokinetic analysis of data was performed using non-compartmental method (Phoenix® WinNonlin® 8.0). This method was performed accurately and reproducibly over a range of 0.05 to 20 µg/mL for FF. The linearity (r) was between 0.9984 and 0.9996. Limit of detection was 0.025 µg/mL; while limit of quantification was 0.05 µg/mL. Furthermore, the method accuracy and precision (intra- and inter assay) were 97.39 % (CV of 11.33 %) and 92.28 % (CV of 8.06%), respectively. Following intramuscular administration, FF was rapidly absorbed. An average Cmax of 3.99 ± 0.57 µg/mL was obtained at 2.33 h (Tmax), the AUC0-∞ was 98.363± 29.010 hr.µg/mL and the mean retention time (MRT) was 36.59± 14.67 h. The development of long-acting formulations is one of the priority aspects for veterinary clinic. The elimination half-life (27.07 ± 9.99 h) obtained after intramuscular FF administration shows a prolonged persistence, fundamental aspect for time-dependent antimicrobials. In our case, after the administration of a single dose of FF, concentrations were maintained above the MIC for Actinobacillus pleuropneumoniae and Pasteurella multocida (0.5 µg/mL) for approximately 40 h and above the MIC for Haemophilus parasuis (1 µg/mL) for 30 h. As a conclusion, the pharmacokinetics of florfenicol in pigs after intramuscular administration of a 30% formulation was characterized by rapid and sustained absorption, extensive distribution and slow elimination.