Pharmacokinetics of Cephalexin after Intravenous and Single and Multiple Intramuscular Administration to Rabbit

Cephalexin is a first generation cephalosporin widely used in rabbits. Its spectrum includes Pasteurella multocida and Staphylococcus aureus. These bacteria, together with Bordetella bronchiseptica, are the main cause of respiratory infections. Although many textbooks on rabbit therapeutics report the use of cephalexin, including administration schedules, there are not published papers on the pharmacokinetics of cephalexin after IV and IM administration to rabbit. Therefore, the objective of the present study was to describe cephalexin disposition in rabbits after intravenous and single and multiple intramuscular administrations. Three administration schedules were studied: single IV administration (10 mg/kg), single IM administration (10 mg/kg) and multiple IM administration (2.5 mg/kg/6). Serial blood samples were collected over a 24 h period. Cephalexin plasma concentrations were determined by microbiological method using Kocuria rhizophila ATCC 9341 as microorganism test. No statistical differences were observed between routes of administration for any of the estimated PK parameters. The unique difference was observed on bioavailability between intramuscular administration schedules. Elimination half-life was 1.45, 1.09 and 1.91 h for the single IV, single IM and multiple IM administration, respectively. Bioavailability after single and multiple IM administration was 47 and 97.5%, respectively. After multiple IM administration maximum and minimum plasma concentration at steady state were 2.77 and 0.34 µg/ml, while Cmax after single IM administration was 9. 22 µg/ml. Considering that for betalactams the PK/PD breakpoint recommended for efficacy (T > MIC) should be 50–80% and that the reported MIC for most gram-positive organisms and Pasteurella multocida is ≤1.0 μg/ml, the present study demonstrates that a single IM dose of 10 mg/kg/24 h is enough to maintain therapeutic concentrations for a 24 hours period. When a 2.5mg/kg dose is used administration every 6 hours is recommended.Fil: Meneses, María Laura. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Albarellos, Gabriela Alejandra. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Biofilms bacterianos

Las poblaciones bacterianas tienen la habilidad de adaptarse rápida y óptimamente a los cambios en los ambientes en los que existen. De esta manera, en ambientes propicios, con ausencia o baja incidencia de factores estresantes, se las puede encontrar de forma individual, también llamada planctónica. Sin embargo, los cambios bruscos en el ambiente que las rodea, conducen a un cambio importante en el comportamiento de la bacteria individual, la cual tiende a contactar y “comunicarse” con las bacterias aledañas para conformar una patina bacteriana, llamada biofilm. Los biofilm son responsables de las infecciones bacterianas crónicas y/o recidivantes en humanos y animales. La característica fundamental de los biofilm bacterianos es su amplia resistencia frente a una variedad de antimicrobianos, la cual es consecuencia de mecanismos distintos a los reportados para la bacteria en estado planctónico. La formación de biofilms comienza a ser reconocida como un proceso de desarrollo multicelular. Esta es la llave de las nuevas estrategias terapéuticas: el cambio del blanco a tratar, dejar de pensar en la bacteria para empezar a pensar en ese organismo multicelular conformado por bacterias al que se denomina biofilm.Bacterial populations have the ability to adapt quickly and optimally to changes in its environment. Thus, in favourable environments, with no or low incidence of stressors, they can be found in individual form also called planktonic. However, sudden changes in the surrounding environment leads to a significant change in the behaviour of the individual bacteria, which tends to contact and “communicate” with neighbour bacteria to form a conglomerate called biofilm. Biofilms are responsible for chronic/recalcitrant infections in humans and animals. The most important feature of bacterial biofilms is their high resistance to a wide range of antimicrobials, by mechanism other than those reported for planktonic bacteria. Biofilms development is beginning to be recognized as a process of multicellular development. This is the key to a new therapeutic strategy: changing the therapeutic target from the planktonic bacteria to this multicellular organism called biofilm.Fil: Meneses, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Landoni, Maria Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Penetration enhancers for the development of intranasal formulations for use in equines

The aim of this review is to assess penetration enhancers, such as cyclodextrins, chitosan and their derivatives, surfactants, bileacids, their salts and derivatives, sodium taurodihidrydrofusidate, and phospholipids used in the development of intranasalformulations with a potential application in horses. In the last few years, the interest in the intranasal administration routein humans has grown because it is bloodless, noninvasive, and painless and represents a direct path toward the centralnervous system. However, in equine medicine, the use of this administration route is scarce. Since equines have a nasal cavitywith large surface area and blood irrigation, a high bioavailability of intranasal administered drugs is expected. Nowadays,the development of formulations for intranasal administration in equines is a challenge. The present review proposes theassessment of the characteristics and potential effects of the most important penetration enhancers in the development ofintranasal formulations for use in equines.Fil: Velloso, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Landoni, Maria Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Penetration enhancers for the development of intranasal formulations for use in equines

The aim of this review is to assess penetration enhancers, such as cyclodextrins, chitosan and their derivatives, surfactants, bileacids, their salts and derivatives, sodium taurodihidrydrofusidate, and phospholipids used in the development of intranasalformulations with a potential application in horses. In the last few years, the interest in the intranasal administration routein humans has grown because it is bloodless, noninvasive, and painless and represents a direct path toward the centralnervous system. However, in equine medicine, the use of this administration route is scarce. Since equines have a nasal cavitywith large surface area and blood irrigation, a high bioavailability of intranasal administered drugs is expected. Nowadays,the development of formulations for intranasal administration in equines is a challenge. The present review proposes theassessment of the characteristics and potential effects of the most important penetration enhancers in the development ofintranasal formulations for use in equines.Fil: Velloso, María Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Landoni, Maria Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Bioavailability of butorphanol after intranasal administration to horses

The aim of the present study was to describe butorphanol pharmacokinetics and bioavailability following intranasal administration to horses. Six adult horses received 0.05 mg/kg butorphanol, in a randomised crossover design, by either intravenous or intranasal route. Plasma concentrations of bu-torphanol were measured at predetermined time points using liquid chromatography/mass spectrome-try assay. After intravenous injection, mean ±SD butorphanol steady-state volume of distribution and clearance was 3.20 ± 1.77 L/kg and 3.18 ± 1.47 L/kg/h, respectively. Terminal half-lives for butor-phanol after intravenous and intranasal administrations were 0.68 ± 0.17 h and 1.79 ± 1.43 h. For intranasal administration, absorption half-life and peak plasma concentration were 0.43 ± 0.33 h and 1.95 ± 1.7 ng/mL, respectively. Bioavailability was 54.45 ± 20.09%. Intranasal butorphanol administration in horses is practical, not stressful and well tolerated. Therefore, it might be a substitute to the intravenous route in adult horses.Fil: Ferreira, V.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Velloso, María Inés. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Pharmacokinetics of erythromycin after intravenous, intramuscular and oral administration to cats

The aim of this study was to characterise the pharmacokinetic properties of different formulations of erythromycin in cats. Erythromycin was administered as lactobionate (4 mg/kg, intravenously (IV)), base (10 mg/kg, intramuscularly (IM)) and ethylsuccinate tablets or suspension (15 mg/kg, orally (PO)). After IV administration, the major pharmacokinetic parameters were (mean ± SD): area under the curve (AUC)(0-∞) 2.61 ± 1.52 µg.h/mL; volume of distribution (Vz) 2.34±1.76 L/kg; total body clearance (Clt) 2.10±1.37 L/h.kg; elimination half-life (t½λ) 0.75±0.09 h and mean residence time (MRT) 0.88±0.13 h. After intramuscular administration, the principal pharmacokinetic parameters were (mean ± DS): peak concentration (Cmax), 3.54±2.16 µg/mL; time of peak (Tmax), 1.22±0.67 h; t½λ, 1.94±0.21 h and MRT, 3.50±0.82 h. The administration of erythromycin ethylsuccinate (tablets and suspension) did not produce measurable serum concentrations. After IM and IV administrations, erythromycin serum concentrations were above minimum inhibitory concentration (MIC)90=0.5 µg/mL for 7 and 1.5 h, respectively. However, these results should be cautiously interpreted since tissue erythromycin concentrations have not been measured and, it is recognised that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.Fil: Albarellos, G. A.. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Montoya, L.. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Clinical efficacy of levofloxacin on the treatment of dogs affected by skin and urinary infections

La eficacia y tolerancia de levofloxacina (Floxaday®, Holliday-Scott) para el tra-tamiento de infecciones dérmicas y de vías urinarias, fue evaluada en caninos. Se inclu-yeron 32 casos clínicos de dermatitis que fueron tratados con 10 mg/kg vía oral cada 24 horas durante 14 y hasta 21 días. De los 14 casos de afecciones a nivel dérmico, 4 fue-ron severos y los restantes de severidad intermedia. De los 12 casos de infecciones a nivel urinario, 8 fueron procesos severos, 3 intermedios y uno bajo. La eficacia de los tratamientos fue evaluada aplicando una escala ad-hoc. El tratamiento fue exitoso en el 99% de los casos, observándose curación clínica al día 4 en el 6,25% y al día 7 en el 43,75%. En el día 14 la curación clínica fue registrada en el 99% de los pacientes; sola-mente uno de ellos requirió un tratamiento de 21 días para alcanzarla. En la población con infecciones urinarias todos los pacientes respondieron satisfactoriamente al trata-miento (curación clínica), el 42% lo hizo hacia el día 4 y el 83% al día 7. Al día 14, la curación clínica fue constatada en el 100% de los casos. No se observaron efectos se-cundarios en ninguno de los pacientes incluidos en el estudio. En caninos, levofloxacina administrada por vía oral a la dosis de 10 mg/kg una vez al día, demostró una excelente eficacia y nula aparición de efectos adversos.The efficacy and tolerance of levofloxacin for the treatment of skin and urinary tract infections were evaluated in canines. Twenty six clinical cases were included and treated orally with 10 mg/kg every 24 hours for 14 to 21 days. From the 14 cases of skin disorders, 4 corresponded to severe cases and the rest to intermediate severity. From the 12 cases of infections at urinary level, 8 corresponded to severe infections, 3 were intermediate and one was low. Treatment was successful in 99% of the cases of dermatitis. Clinical cure (score 0) was observed at day 4 for 6.25% and day 7 for 43.75% of the animals, respectively. By day 14 clinical cure was observed in 99% of patients. One patient required a 21-day treatment to reach score 0. In the population with urinary infections, all patients responded satisfactorily to treatment (clinical cure-score 0), 42% on day 4 and 83% on day 7. By day 14 clinical cure was observed in 100% of patients. No side effects were observed in any of the patients included in the study. Levofloxacin (Floxaday®, Holliday-Scott) administered orally at a dose of 10 mg/kg once a day in canines, demonstrated excellent efficacy with no adverse effects.Fil: Casas, L.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Vaz, S.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Pharmacodynamics, chiral pharmacokinetics and PK–PD modelling of ketoprofen in the goat

There have been few studies of the pharmacodynamics of nonsteroidal antiinflammatory drugs (NSAIDs) using PK–PD modelling, yet this approach offers the advantage of defining the whole concentration–effect relationship, as well as its time course and sensitivity. In this study, ketoprofen (KTP) was administered intravenously to goats as the racemate (3.0 mg/kg total dose) and as the single enantiomers, S(+) KTP and R(−) KTP (1.5 mg/kg of each). The pharmacokinetics and pharmacodynamics of KTP were investigated using a tissue cage model of acute inflammation. The pharmacokinetics of both KTP enantiomers was characterized by rapid clearance, short mean residence time (MRT) and low volume of distribution. The penetration of R(−) KTP into inflamed (exudate) and noninflamed (transudate) tissue cage fluids was delayed but area under the curve values were only slightly less than those in plasma, whereas MRT was much longer. The S(+) enantiomer of KTP penetrated less readily into exudate and transudate. Unidirectional inversion of R(−) to S(+) KTP occurred. Both rac-KTP and the separate enantiomers produced marked inhibition of serum thromboxane B2 (TxB2) synthesis (ex vivo) and moderate inhibition of exudate prostaglandin E2 (PGE2) synthesis (in vivo); pharmacodynamic variables for S(+) KTP were Emax (%) = 94 and 100; IC50 (μg/mL) = 0.0033 and 0.0030; N = 0.45 and 0.58, respectively, where Emax is the maximal effect, IC50 the plasma drug concentration producing 50% of Emax and N the slope of log concentration/effect relationship. The IC50 ratio, serum TxB2:exudate PGE2 was 1.10. Neither rac-KTP nor the individual enantiomers suppressed skin temperature rise at, or leucocyte infiltration into, the site of acute inflammation. These data illustrate for KTP shallow concentration–response relationships, probable nonselectivity of KTP for cyclooxygenase (COX)-1 and COX-2 inhibition and lack of measurable effect on components of inflammation

Effects of treatment with florfenicol in the control of bovine respiratory disease in feed-lots

El objetivo del presente ensayo fue evaluar la eficacia deltratamiento metafiláctico con dosis únicas de florfenicol (20 y40 mg/kg vía subcutánea) frente a la enfermedad respiratoriaen terneros en engorde a corral. Se incluyeron 1.297 terneros,machos y hembras, con peso promedio de 110 kg, divididosen 5 corrales. Los animales fueron asignados, al azar, en tresgrupos; florfenicol 20 mg/kg (FLO20), florfenicol 40 mg/kg (FLO40)mientras que el tercer grupo, control, no recibió tratamiento(CTL). Se registró el peso individual de cada uno de los gruposen estudio (n=30 por grupo) los días 0, 21 y 50 del ensayo.El diseño fue en bloque (corral) y el animal fue consideradola unidad experimental. El porcentaje de animales enfermosfue de 10,83; 3,48 y 2,31 para los grupos CTL, FLO20 y FLO40,respectivamente. Además, se observó en los primeros 21 díasdel ensayo, una mayor ganancia diaria de peso (p<0,001) enlos grupos FLO20 y FLO40. El tratamiento metafiláctico con FLOdisminuyó la morbilidad por enfermedad respiratoria y mejoróla ganancia diaria de peso. No se encontraron diferenciasestadísticamente significativas entre los grupos FLO20 y FLO40en la ganancia diaria, incidencia de enfermedad respiratoria,porcentaje de retratamientos, ni mortalidadThe aim of this study was to evaluate the efficacy of metaphylactic treatment with single doses of florfenicol (20 and 40 mg/kg subcutaneously), against respiratory disease in feedlot calves. A total of 1297 male and female calves with an average weight of 110 kg were placed in five pens. They were randomly assigned to three groups: one group treated with florfenicol SC 20mg/kg (FLO20), a group treated with florfenicol SC 40 mg/kg (FLO40) and the control group (CTL) received no treatment. Individual weight was obtained in each group (n=30) on days 0, 21 and 50 of the trial. A complete randomize block (pen) design was used and the animal was considered the experimental unit. The percentage of ill animals was 10.83, 3.48 and 2.33 for the CTL, FLO20 and FLO40 groups, respectively. Moreover, a higher daily weight gain was observed in the FLO20 and FLO40 groups within the first 21 days of the trial (p<0,001). Metaphylactic treatment with FLO reduced morbidity due to respiratory disease and improved daily weight gain. No statistically significant differences were found between FLO20 and FLO40 groups regarding daily weight gain, respiratory bovine disease incidence, retreatment or mortality.Fil: Galvan, Walter Ruben. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Arriaga, Guido José. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Streitenberger, Nicolás. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Fazzio, Luis Emilio. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Intranasal drug delivery: an alternative for the administration of central acting drugs in horses

La vía intranasal es reconocida en medicina humana como una vía muy promisoria para la administración sistémica y cerebral de fármacos. Es una vía de administración indolora, incruenta, económica, y práctica. Por sus características, es muy útil para la aplicación de fármacos en pacientes con alteraciones orales, con diarrea o que no cooperen. Además, es una potencial vía directa al sistema nervioso central (SNC). Su uso en medicina veterinaria es muy raro, salvo para la administración de tratamientos locales. En la especie equina, aun cuando no hay estudios completos y profundos sobre las características anatomofisiológicas de la cavidad nasal, su gran superficie e irrigación (área potencial de absorción) permiten inferir su viabilidad para la administración sistémica de fármacos. En el presente artículo se discuten las características de la cavidad nasal de los equinos en relación a las diversas vías de absorción sistémica y del transporte nariz-cerebro de fármacos, así como las potenciales aplicaciones de esta vía de administración.The intranasal route is recognized as a very promising route for the systemic and cerebral administration of drugs in human medicine. It is a painless, non­invasive, economical, and practical administration route. Due to its characteristics, it is very useful for the application of drugs in non­cooperative patients, as well as those with oral alterations or diarrhoea or, being a potential direct route to the central nervous system (CNS). However, its use in veterinary medicine is very rare, except for the administration of local treatments. Even though there are no complete and thorough studies on the anatomophysiological characteristics of the nasal cavity in the equine species, its large surface area and irrigation and consequent potential absorption area suggest a promising alternative for the systemic administration of drugs. In the present article, the characteristics of the nasal cavity of horses in relation to the various routes of systemic absorption and nose­brain passage of drugs are discussed, as well as the potential applications of this route of administration.Fil: Ferreira, Violeta. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Hospital Escuela; ArgentinaFil: Velloso, María Inés. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Vita, Mariangeles. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Landoni, Maria Fabiana. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin