Cárceles Rodríguez, Carlos

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Cárceles Rodríguez, Carlos

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Cárceles Rodríguez, Carlos

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Universidad de Murcia. Departamento de Farmacología

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Open Access
Ethnoveterinary medicine and Ethnopharmacology in the main transhumance areas of Castilla-La Mancha (Spain)
(Frontiers Media, 2022-05-03) Rivera Núñez, Diego; Verde, Alonso; Fajardo Rodríguez, José; Ríos, Segundo; Alcaraz Ariza, Francisco José; Cárceles Rodríguez, Carlos; Ortiz Sánchez, Juana María; Valdés, Arturo; Ruíz-Gallardo, José Reyes; García-Flores, Aida; Palazón Ferrando, José Antonio; Obón, Concepción; Sanidad Animal
In this study, we document the practices of ethnoveterinary medicine and ethnopharmacology in the context of traditional transhumance routes that cross Castilla La Mancha from north to south. Transhumance is a type of grazing system that allows advantage to be taken of winter pastures (wintering places) and summer pastures by seasonal movement, twice a year, of cattle and their shepherds. Our study is based on over 200 interviews (from 1994 to 2021) conducted in 86 localities along eight major transhumance routes “cañadas reales” and 25 other minor transhumance routes, and involved 210 informants, 89 single and 121 groups, and 562 individuals, of which the majority were men. Sixty-three recorded pathologies and their treatments are discussed. Two hundred and two species and substances, belonging to 92 different families, have been recorded from the interviews, of which most are plants. Amid the toxic plant species, the most cited in the interviews are Erophaca baetica (L.) Boiss., Lupinus angustifolius L., and Oenanthe crocata L. Some of the species reported as toxic were reservoirs of pathogens or markers for dangerous areas. One of the fields most widely covered in our study is that of prevention, protection, and control of endo- and ectoparasites. This control is carried out mainly by means of aromatic plants. As a polyvalent species, Daphne gnidium L. is outstanding, and it contributes one-tenth of the records of our study. Among the species of fundamentally therapeutic use, Cistus ladanifer L. stands out by far. Principal Coordinate Analysis (PCoA) based on the repertories of ingredients, separates the routes whose most important sections run through siliceous terrain with its characteristic flora, especially in the provinces of Ciudad Real and Toledo, from the routes that run through the limestone terrain of Albacete and Cuenca, and link the Eastern Mancha and the “Serranía de Cuenca” with Andalusia and the Spanish Levant.
Open Access
Pharmacokinetic/pharmacodynamic modeling in plasma and milk and Mote Carlo simulations of marbofloxacin against Staphylococcu aureus and Mycoplasma agalactie in lactating sheep
(Elsevier, American Dairy Science Association, 2025-03-24) Serrano-Rodríguez, J. M.; Fernández-Varón, E.; Muñoz-Rascón, P.; Morón, R.; Díaz-Villamarín, X.; Fé Rodríguez, David Christian de la; Cárceles-García, C.; Cárceles Rodríguez, Carlos; Farmacología; Facultad de Veterinaria
In livestock ruminants such as sheep, different infectious diseases such as mastitis or contagious agalactia are originated from pathogens as Staphylococcus aureus and Mycoplasma agalactiae. Fluoroquinolones are authorized in dairy animals, including their extralabel use, as an alternative when other treatment failed in the European Union (EU), however, in the United States, are prohibited from extralabel drug use in food-producing animals. Marbofloxacin, a well-known fluoroquinolone is commonly used in dairy cattle in the EU at 10 mg/kg. However, their off-label use in sheep also has been described. Nevertheless, the dose extrapolations from dairy cows should include pharmacokinetic (PK) studies because of interspecies differences and the potential risks of antimicrobial resistance or toxicity. In this regard, the aims of this research were to (1) describe the i.v. and i.m. PK analysis of marbofloxacin in plasma and milk of lactating sheep at 10 mg/kg, (2) determine the MIC and calculate the tentative epidemiological cutoff values (TECOFF) for Mycoplasma agalactiae and Staphylococcus aureus wild-type isolates from sheep, and (3) conduct a pharmacokinetic and pharmacodynamic (PK/PD) analysis with the Monte Carlo simulation to obtain the probability of target attainment for different MIC values, known as the PK/PD cutoff values. The results of this study could help to establish the efficacy of a 10 mg/kg dosage regimen of marbofloxacin in lactating sheep. Plasma and milk concentrations were described with a nonlinear mixed effects model. The intramuscular biobioavailability was 88%, and the volume of distribution was 1.31 L/kg with a clearance value of 0.38 L/h/kg. Halflives after i.v. and i.m. dosing were 6.53 and 7.09 h in plasma, and 6.62 and 6.65 h in milk, respectively. High concentrations were determined in milk with area under the curve (AUC) milk/plasma ratios close to 1.28. The MIC values for Staphylococcus aureus and Mycoplasma agalactiae were obtained, and TECOFF values of 1.0 and 2.0 μg/mL, respectively, were determined. The Monte Carlo simulations predicted that the dosage regimen of 10 mg/kg per 24 h in lactating sheep can be adequate for intermediate and high MIC values of 0.5 and 1.0 μg/mL, respectively, and could be useful for populations with a target AUC/MIC ratio ≤48 for Staphylococcus aureus, but not for Mycoplasma agalactiae. Results derived for this study could be taken as previous tentative points for further studies of marbofloxacin in lactating and nonlactating sheep in a clinical context.
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Population pharmacokinetics and pharmacokinetic/pharmacodynamic evaluation of marbofloxacin against Coagulase-negative staphylococci, Staphylococcus aureus and Mycoplasma agalactie pathogens in goats
(Elsevier, 2023-04-03) Serrano-Rodríguez, Juan Manuel; Fernández-Varón, Emilio; Cárceles Rodríguez, Carlos; San Andrés-Larrea, Manuel Ignacio; Rubio-Langre, Sonia; Fé Rodríguez, David Christian de la; Waxman Dova, Samanta; Bhardwaj, Pallavi; Sidhu, Pritam Kaur; Litterio, Nicolás Javier; Lorenzutti, Augusto Matías; Farmacología; Facultad de Veterinaria
Marbofloxacin is a broad-spectrum fluoroquinolone, and an extra-label use has been reported in horse, sheep and goat. However, extrapolation of dosage regimens from cattle to horse and small ruminants could lead to incorrect dosing due to pharmacokinetic differences among species, increasing the risk of antimicrobial resistance or toxicity. Pharmacokinetic properties of marbofloxacin, including PK/PD analysis, have been studied by intravenous, intramuscular and subcutaneous administration in lactating and non-lactating goats. A population pharmacokinetic model of marbofloxacin in goats was built using 10 pharmacokinetic studies after intravenous, intramuscular, and subcutaneous administration at a dose of 2, 5 and 10 mg/kg. Serum or plasma and milk concentration-time profiles were simultaneously fitted with a non-linear mixed effect model with Monolix software. Level of milk production (lactating and non-lactating) and health status (healthy and un-healthy) were retained as covariates on volume of distribution and clearance. Marbofloxacin concentrations were well described in plasma/serum and milk by the population model. Simulated dose regimens of marbofloxacin administered at 2, 5 and 10 mg/kg by intramuscular route for five days were evaluated (n = 5000 per group). Steady-state fAUCs for each dose regimen were obtained. Probability of target attainment of fAUC/MIC ratios were determined and PK/PDco values (highest MIC for which 90% of individuals can achieve a prior numerical value of the fAUC/MIC index) were established using Monte Carlo simulations (n = 50,000). MIC values for wild type isolates of Staphylococcus aureus, coagulase negative staphylococci, and Mycoplasma agalactiae were determined and tentative epidemiological cutoff (TECOFF) were obtained at 1.0, 0.5 and 0.5 mg/L, respectively. The PK/PDco for the dose regimen of 2 mg/kg/24 h and 5 mg/kg/24 h (0.125 and 0.25 mg/L) were lower than TECOFF (0.5 and 1 mg/L). The dosage regimen of 10 mg/kg/24 h was adequate for intermediate MIC values of 0.125–0.50 mg/L and could be effective for a population with a target fAUC/MIC ratio ˂ 48 for Coagulase negative staphylococci and Mycoplasma agalactiae, but not for Staphylococcus aureus. Results obtained in this study could be taken as a starting point by committees that set the clinical breakpoints and justifies expert rules to optimize marbofloxacin dose regimens.
Open Access
Empleo del cannabidiol (CBD) en la osteoartrosis canina
(Facultad de Veterinaria y el Servicio de Publicaciones de la Universidad de Murcia, 2023-12-29) Lara Herrera, Víctor; Cárceles Rodríguez, Carlos; Farmacología; Facultad de Veterinaria
La planta Cannabis sativa está formada por una gran variedad de principios activos, que reciben el nombre de cannabinoides. Existen 3 tipos diferentes de cannabinoides: los endocannabinoides, los fitocannabinoides y los cannabinoides sintéticos. Este estudio se centra en el desarrollo del CBD, puesto que es un producto que produce mínimos o nulos efectos psicoactivos y carece de toxicidad frente a los animales.La gran mayoría de los animales presentan un sistema endocannabinoide, formado por agonistas endóge-nos y sus receptores. Asimismo, fisiológicamente interviene en la regulación de la analgesia, el aprendizaje, la actividad locomotora, la ansiedad, el apetito, la motilidad gastrointestinal, el control inmune y la función cardiovascular. El CBD actúa en multitud de receptores en el organismo produciendo una gran diversidad de acciones terapéuticas.La osteoartrosis es una enfermedad autodegenerativa articular, cuyo principal signo clínico es el dolor. Actual-mente, el manejo farmacológico de la OA puede no producir una correcta analgesia y generar efectos indeseables. En este estudio se propuso como principal objetivo determinar si el CBD podría ser una alternativa en el tratamiento de la OA o bien utilizarse conjunto a un tratamiento multimodal. Para ello, se escogieron 5 artículos diferentes. Los resultados de los estudios demostraron que el CBD disminuía notablemente la sensación de dolor y me-joraba la calidad de vida. No se observaron signos clínicos secundarios a su administración, a excepción de un aumento de la fosfatasa alcalina. Existiendo la posibilidad de que el uso del CBD pudiera ocasionar daño hepático. Las conclusiones que se pueden sacar de este estudio es que el CBD es un producto que presenta un gran potencial terapéutico, una dosis efectiva mínima y mínimos efectos adversos. Demostrando ser un fármaco muy completo, que necesita más estudios para poder utilizarse de manera más amplia y sin riesgos
Open Access
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) Fernández-Varón, Emilio; García Romero, Edgar; Serrano-Rodriguez, Juan M.; Cárceles Rodríguez, Carlos; García-Galán Pérez, Ana; Cárceles-García, Carlos; Fernández, Rocío; Muñoz, Cristina; Fé Rodríguez, David Christian de la; 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.