Determinação do perfil farmacocinético de ciprofloxacina administrada por via intramuscular em bezerras Holandesas

Abstract

Ciprofloxacin is a fluoroquinolone approved by the Brazilian Ministry of Agriculture, Livestock, and Food Supply (MAPA) for the treatment of respiratory, urinary, enteric, cutaneous infections, and mastitis in cattle. Although enrofloxacin is the most commonly used drug in ruminants, ciprofloxacin—its active metabolite—shows high antimicrobial activity against relevant pathogens such as Escherichia coli, Salmonella spp., Mannheimia haemolytica, Pasteurella multocida, and Mycoplasma spp. This study aimed to characterize the pharmacokinetic profile of ciprofloxacin following intramuscular administration in Holstein heifers and to evaluate the efficacy of different dosing regimens by integrating pharmacokinetic and pharmacodynamic (PK/PD) parameters. Twelve healthy animals were used, each receiving a single intramuscular dose of 2.5 mg/kg of ciprofloxacin. Plasma concentrations were quantified by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Population pharmacokinetic modeling was performed using a one-compartment model with first-order absorption and linear elimination, estimating the following parameters: Ka (17.49 h−1), volume of distribution (257.8 L/kg), and clearance (51.38 L/kg/h), with high interindividual variability observed. Monte Carlo simulations were conducted for doses of 2.5, 5, 7.5, and 10 mg/kg, considering a range of minimum inhibitory concentrations (MIC) between 0.03 and 2 μg/mL, and incorporating the interindividual variability of the estimated pharmacokinetic parameters to assess the probability of target attainment (PTA) based on PK/PD indices established for fluoroquinolones (Cmax/MIC ≥ 10 and fAUC/MIC ≥ 125). The results indicate that the 2.5 mg/kg dose provides high PTA for microorganisms with MIC below 0.125 μg/mL, while higher doses are required to ensure efficacy against pathogens with higher MICs. This study provides fundamental data for optimizing ciprofloxacin therapeutic regimens in heifers, contributing to the rational use of antimicrobials and mitigation of bacterial resistance in veterinary practice.