Browsing by Subject "Long-acting formulation"

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    Pharmacokinetic/Pharmacodynamic Modelling of Cefquinome in Lactating Sheep and Lactating Goats After Intravenous, Subcutaneous and Long-Acting Administrations
    (MDPI, 2026-06-13) Cárceles Rodríguez, Carlos; Cristina Bernal Alcaraz; Carlos Cárceles García; Rocío Morón Romero; Xando Díaz Villamarín; Pilar Muñoz Rascón; Fernández Varón, Emilio; Serrano Rodríguez, Juan Manuel; Farmacología; Facultades de la UMU::Facultad de Veterinaria
    Cefquinome is a fourth-generation cephalosporin widely used in veterinary medicine, although its pharmacokinetic (PK) properties and optimal dose regimen remain insufficiently characterized in small ruminants. In particular, limited information is available regarding the influence of different formulations on drug disposition and therapeutic effectiveness. This study investigated the PK and the pharmacokinetic–pharmacodynamic (PK/PD) relationships of cefquinome in lactating sheep and goats following intravenous, subcutaneous and long-acting (LA) subcutaneous administration, using nonlinear mixed effect models (NLMEs) and Monte Carlo (MC) simulations as modelling and simulation techniques, respectively. Our findings demonstrate that despite the interspecies differences observed, the LA formulation markedly prolongs drug exposure in both species by slowing absorption and increasing the terminal half-life. This sustained exposure translates into improved probability of target attainment (PTA) against bacterial pathogens. Importantly, the results also suggest differences in the PK/PD index of efficacy: while the percentage of time above the minimum inhibitory concentration (fT > MIC) is traditionally used for beta-lactams, the ratio of the area of free concentrations under the curve (fAUC/MIC) appears to better describe efficacy for LA formulations. Finally, lower concentrations were observed in milk below the limits of quantification. Overall, these findings highlight that LA formulation may enhance therapeutic outcomes and support more effective and rational antimicrobial use in small ruminants, particularly in the treatment of respiratory infections.
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    PK/PD analysis of marbofloxacin by Monte Carlo Simulation against Mycoplasma agalactie in plasma and milk of lactating goats after IV, SC and SC-long acting formulations administration
    (MDPI, 2021-04-12) García Romero, Edgar; Cárceles Rodríguez, Carlos; García-Galán Pérez, Ana; Cárceles-García, Carlos; Fernández, Rocío; Muñoz, Cristina; Fé Rodríguez, David Christian de la; Fernández Varón, Emilio; Serrano Rodríguez, Juan Manuel; Farmacología; Facultad de Veterinaria
    Contagious agalactia is a mycoplasmosis affecting small ruminants that have become an important issue in many countries. However, PK/PD studies of antibiotics to treat this problem in lactating goats affected by Mycoplasma (M.) agalactiae, the main CA-causing mycoplasma are almost non-existent. The aims of this study were to evaluate the plasma and milk disposition of marbofloxacin in lactating goats after intravenous (IV), subcutaneous (SC) and subcutaneous poloxamer P407 formulations with and without carboxy-methylcellulose (SC-P407-CMC and SC-P407) administration. Marbofloxacin concentrations were analysed by the High Performance Liquid Chromatography (HPLC) method. Minimum inhibitory concentrations (MIC) of M. agalactiae field isolates from mastitic goat’s milk were used to calculate surrogate markers of efficacy. Terminal half-lives of marbofloxacin after IV, SC, SC-P407 and SC-P407-CMC administration were 7.12, 6.57, 13.92 and 12.19 h in plasma, and the half-lives of elimination of marbofloxacin in milk were 7.22, 7.16, 9.30 and 7.74 h after IV, SC, SC-P407 and SC-P407-CMC administration, respectively. Marbofloxacin penetration from the blood into the milk was extensive, with Area Under the Curve (AUCmilk/AUCplasma) ratios ranged 1.04–1.23, and maximum concentrations (Cmax-milk/Cmax-plasma) ratios ranged 0.72–1.20. The PK/PD surrogate markers of efficacy fAUC24/MIC and the Monte Carlo simulation show that marbofloxacin ratio (fAUC24/MIC > 125) using a 90% of target attainment rate (TAR) need a dose regimen between 8.4 mg/kg (SC) and 11.57 mg/kg (P407CMC) and should be adequate to treat contagious agalactia in lactating goats.