Estudo farmacocinético de cloxacilina benzatina em caprinos saudáveis

Abstract

The search for safe and effective therapeutic alternatives has driven the development of innovative formulations for use in goats, given the scarcity of approved veterinary drugs for this species. In this context, the use of nanostructures applied to antimicrobials represents a promising strategy, with the potential to enhance bioavailability, prolong drug release, and optimize tissue distribution. In addition to formulation improvements, new approaches related to parenteral administration routes have been explored in goats. This study was conducted in two distinct phases, aiming to characterize and compare the pharmacokinetic profiles of different benzathine cloxacillin formulations in healthy goats. In the first phase, a nanostructured formulation was evaluated following subcutaneous administration at a dose of 4 mg/kg. In the second phase, the conventional formulation was investigated following intramuscular administration at doses ranging from 2 to 20 mg/kg. Six clinically healthy female goats, crossbred from Saanen and Anglo/Nubian breeds, were used. Serial blood samples were collected for up to 24 hours post-administration. Plasma concentrations were quantified by Ultra Performance Liquid Chromatography coupled with Tandem Mass Spectrometry (UPLC-MS/MS). Population pharmacokinetic modeling was performed using Monolix 2024R1 software. The pharmacokinetic modeling conducted in both phases of the study enabled a deeper understanding of the behavior of the distinct cloxacillin formulations in goats. The findings represent a relevant advance for veterinary medicine, highlighting the potential of these formulations to optimize the use of antimicrobials with lower critical importance to human health, in accordance with the World Health Organization (WHO) guidelines for combating antimicrobial resistance. This study supports future investigations aimed at evaluating the clinical efficacy of cloxacillin and integrating PK/PD indices in animals affected by susceptible etiological agents.