Avaliação da farmacocinética do levofloxacino em equinos e do perfil antibacteriano para construção do regime posológico
Carregando...
Data
2021-10-27
Autores
Martins Teodoro, Evelin dos Santos [UNESP]
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O levofloxacino (LEV) é um antimicrobiano da classe fluoroquinolona, que pode ser eficaz em diversos tratamentos de infecções em equinos envolvendo bactérias Gram-negativas e algumas Gram-positivas. Entretanto, é comum na medicina veterinária, extrapolação empírica dos regimes posológicos humanos, o que pode levar ao uso inadequado do medicamento e contribuir para o desenvolvimento de resistência bacteriana. Com o objetivo de projetar um regime posológico racional, o LEV foi estudado em cavalos (n=6) após administração intravenosa e oral de uma dose única de 4 mg/kg. As concentrações do fármaco no plasma foram determinadas por cromatografia líquida de alta eficiência (CLAE) acoplado a um detector de espectrometria de massa. Através de análise compartimental, foram determinados os parâmetros farmacocinéticos. A concentração necessária para inibir 90% dos isolados bacterianos (CIM90) foi avaliada para cepas padrão de bactérias comuns em infecções equinas. Os valores dos índices de eficácia antimicrobiana (ASC/CIM, CMÁX/CIM, T>CIM) foram calculados e usados para determinar regimes de posológicos racionais para bactérias alvo. O clearance do LEV foi 6,86 ± 2,09 mL/min/kg e a meia-vida terminal de 3,84 ± 0,52 horas. A biodisponibilidade absoluta do LEV após administração oral foi de 73 ± 19%. A CIM90 foi de 0,016 μg/mL para E. coli, 0,25 μg/mL para S. aureus e Salmonella spp. e 0,625 μg/mL para P. aeruginosa. Considerando os valores dos pontos de corte dos índices de eficácia, um regime de dosagem de LEV de 4 mg/kg/dia é apropriado para tratar infecções por microrganismos Gram-negativos com CIM90 ≤0,08 μg/mL pela via oral e com CIM90 ≤0,11 μg/mL pela via intravenosa, assim como, tratar infecções por microrganismos Gram-positivos com CIM90 ≤0,21 μg/mL e 0,29 μg/mL pela via oral e intravenosa, respectivamente. Porém, é necessário um regime posológico com doses de 8,95 mg/kg/dia (via oral) e 12,26 mg/kg/dia (via intravenosa) para S. aureus e de 22,38 mg/kg/dia (via oral) e 30,66 mg/kg/dia (via intravenosa) para P. aeruginosa. Concluímos que, devido ao seu amplo espectro de atividade e comportamento farmacocinético favorável, o LEV tem potencial para tratar uma ampla variedade de infecções bacterianas em equinos.
Levofloxacin (LEV) is a fluoroquinolone antimicrobial, which can be effective in several treatments of Gram-negative and some Gram-positive bacterial infections in horses. However, empirical extrapolation of human dosage regimen is common in veterinary medicine, which might lead to inappropriate use of the drug and contribute to the development of bacterial resistance. In order to design a rational dosage regimen, LEV was studied in horses (n=6) after intravenous and oral administration of a single dose of 4 mg/kg. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) – tandem mass spectrometry detection method. The pharmacokinetic data were analyzed by a compartmental analysis. The minimum inhibitory concentration required to inhibit 90% of the bacteria (MIC90) were assessed for standard strains bacteria common in equine infectious. The values of the antimicrobial efficacy indices (ASC/CIM, CMÁX/CIM, T>CIM) were calculated. These data were used to determine rational dosage regimen for target bacteria. The clearance of LEV was 6.86 ± 2.09 mL/min/kg and the terminal half-life was 3,84 ± 0,52 hours. The absolute bioavailability of LEV after oral administration was 73 ± 19%. The CIM90 was 0.016 μg/mL for E. coli, 0.25 μg/mL for S. aureus and Salmonella spp. and 0.625 μg/mL for P. aeruginosa. Considering the breakpoints values of the efficacy indices, a LEV dosage regimen of 4 mg/kg/day is appropriate to treat infections by Gram-negative microorganisms with MIC90 ≤0.08 μg/mL by oral administration and with CIM90 ≤0.11 μg/mL by intravenous administration, as well as, treating infections by Gram-positive microorganisms with MIC90 ≤0.21 μg/mL and 0.29 μg/mL by intravenous and oral administration, respectively. However, a dosage regimen with doses of 8.95 mg/kg/day (orally) and 12.26 mg/kg/day (intravenously) for S. aureus and 22.38 mg/kg/day (orally) and 30.66 mg/kg/day (intravenously) for P. aeruginosa. We concluded that, due to its broad spectrum of activity and favorable pharmacokinetic behavior, LEV has the potential to treat a wide variety of bacterial infections in horses.
Levofloxacin (LEV) is a fluoroquinolone antimicrobial, which can be effective in several treatments of Gram-negative and some Gram-positive bacterial infections in horses. However, empirical extrapolation of human dosage regimen is common in veterinary medicine, which might lead to inappropriate use of the drug and contribute to the development of bacterial resistance. In order to design a rational dosage regimen, LEV was studied in horses (n=6) after intravenous and oral administration of a single dose of 4 mg/kg. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) – tandem mass spectrometry detection method. The pharmacokinetic data were analyzed by a compartmental analysis. The minimum inhibitory concentration required to inhibit 90% of the bacteria (MIC90) were assessed for standard strains bacteria common in equine infectious. The values of the antimicrobial efficacy indices (ASC/CIM, CMÁX/CIM, T>CIM) were calculated. These data were used to determine rational dosage regimen for target bacteria. The clearance of LEV was 6.86 ± 2.09 mL/min/kg and the terminal half-life was 3,84 ± 0,52 hours. The absolute bioavailability of LEV after oral administration was 73 ± 19%. The CIM90 was 0.016 μg/mL for E. coli, 0.25 μg/mL for S. aureus and Salmonella spp. and 0.625 μg/mL for P. aeruginosa. Considering the breakpoints values of the efficacy indices, a LEV dosage regimen of 4 mg/kg/day is appropriate to treat infections by Gram-negative microorganisms with MIC90 ≤0.08 μg/mL by oral administration and with CIM90 ≤0.11 μg/mL by intravenous administration, as well as, treating infections by Gram-positive microorganisms with MIC90 ≤0.21 μg/mL and 0.29 μg/mL by intravenous and oral administration, respectively. However, a dosage regimen with doses of 8.95 mg/kg/day (orally) and 12.26 mg/kg/day (intravenously) for S. aureus and 22.38 mg/kg/day (orally) and 30.66 mg/kg/day (intravenously) for P. aeruginosa. We concluded that, due to its broad spectrum of activity and favorable pharmacokinetic behavior, LEV has the potential to treat a wide variety of bacterial infections in horses.
Descrição
Palavras-chave
Antimicrobianos, fluoroquinolonas, levofloxacino, veterinária, equinos, farmacocinética, farmacodinâmica, regime posológico, fluoroquinolones, One Health, HPLC, pharmacokinetics, pharmacodynamics, dosage regimen, Antimicrobials, fluoroquinolones, veterinary