The pharmacokinetics and metabolism of ivermectin in domestic animal species

P. 25-37The pharmacokinetic properties of drugs are closely related to their pharmacological efficacy. The kinetics of ivermectin are characterised, in general terms, by a slow absorption process, a broad distribution in the organism, low metabolism, and slow excretion. The kinetics vary according to the route of administration, formulation, animal species, body condition, age, and physiological status, all of which contribute to differences in drug efficacy. Characterisation of ivermectin kinetics can be used to predict and optimise the value of the parasiticide effects and to design programmes for parasite control. This article reviews the pharmacokinetics of ivermectin in several domestic animal species.S

Cell death during the postnatal morphogenesis of the normal rabbit kidney and in experimental renal polycystosis

We have studied, by means of optic and electron microscopy, the normal and abnormal cell death that takes place during the postnatal morphogenesis of rabbit kidney, and in the experimental renal polycystosis produced by methylprednisolone acetate. In the normal kidney intertubular cell death can be observed during the first 20 days of the postnatal development. However, cell death in the normal metanephric blastema is a very rare event. In the polycystic kidney numerous dead cells can be seen between the third and forty eighth days after injection. The topography and morphology of the dead cells depend on the stage in the evolution of the disease. In the 'stage of renal immaturity', dying and dead cells are present in the nephrogenic tissue, in the dilating collecting tubules and in the intertubular spaces. In this stage the cellular pathology is essentially nuclear. In the stage of tubular cysts, the dead cells are mostly located in the walls of cysts, with some dead cells, but mostly cellular debris in their lumina. At this stage the cellular pathology is basically cytoplasmic. The dead cells are eventually digested by what appear to be phagocytes of tubular epithelial origin. It is suggested that cell death is an important factor in the evolution of the lesions of renal polycystosis induced by corticosteroids, and probably in the initiation of the pathological process as wel

The Pharmacokinetics and interactions of ivermectin in humans—A mini-review

P. 42-46Ivermectin is an antiparasitic drug with a broad spectrum of activity, high efficacy as well as a wide margin of safety. Since 1987, this compound has a widespread use in veterinary medicine and it use has been extended in humans. Here we present a brief review of the information availabile regarding the pharmacokinetics and interactions of ivermectin in humans. Awareness of these characteristics could improve the clinical efficacy of Ivermectin. All Authors declare that they do not have any Conflict of interest and that the work is original. All Authors agree that the contents of the manuscript are confidential and will not be copyrighted, submitted, or published elsewhere (including the Internet), in any language, while acceptance by the Journal is under consideration.S

The hydrosoluble fiber Plantago ovata husk improves levodopa (with carbidopa) bioavailability after repeated administration

P. 15-20The influence of treatment duration (7 or 14 days) with Plantago ovata husk/levodopa/carbidopa in the bioavailability and other pharmacokinetic parameters of levodopa were evaluated in rabbits. Fiber was administered at two different doses, 100 and 400 mg/kg, and the dosage of levodopa/carbidopa was 20:5 mg/kg. These doses were administered once a day. When 100 mg/kg of fiber was administered, the mean AUC value obtained for levodopa increased 20.2% from day 1 to day 7, and 27.2% from day 1 to day 14; Cmax was 8.6% higher on day 7 and 11.7% higher on day 14. When administering 400 mg/kg of fiber, the increase in AUC values was 17.6% on day 7 and 24.9% on day 14, and that of Cmax 11.1% on day 7 and 11.3% on day 14. The concentration determined immediately before drug administration (Cmin) increased progressively with the duration of treatment, and the highest increase (53.2%) was observed on day 14 with 100 mg/kg of fiber. There was also a delay in levodopa elimination (higher MRT and lower Cl) in a fiber-dose dependent manner. In summary, we found that there was an improvement in the extent of levodopa absorbed with higher final concentrations and that levodopa elimination was slower with the administration of P. ovata husk.S

Pharmacokinetics of doxycycline in sheep after intravenous and oral administration

P. 389-395The pharmacokinetics of doxycycline were investigated in sheep after oral (PO) and intravenous (IV) administration. The IV data were best described using a 2- (n = 5) or 3- (n = 6) compartmental open model. Mean pharmacokinetic parameters obtained using a 2-compartmental model included a volume of distribution at steady-state (Vss) of 1.759 ± 0.3149 L/kg, a total clearance (Cl) of 3.045 ± 0.5264 mL/ kg/min and an elimination half-life (t1/2b) of 7.027 ± 1.128 h. Comparative values obtained from the 3-compartmental mean values were: Vss of 1.801 ± 0.3429 L/kg, a Cl of 2.634 ± 0.6376 mL/kg/min and a t1/2b of 12.11 ± 2.060 h. Mean residence time (MRT0_1) was 11.18 ± 3.152 h. After PO administration, the data were best described by a 2-compartment open model. The pharmacokinetic parameter mean values were: maximum plasma concentration (Cmax), 2.130 ± 0.950 lg/mL; time to reach Cmax (tmax), 3.595 ± 3.348 h, and absorption half-life (t1=2k01 ), 36.28 ± 14.57 h. Non-compartmental parameter values were: Cmax, 2.182 ± 0.9117 lg/mL; tmax, 3.432 ± 3.307 h; F, 35.77 ± 10.20%, and mean absorption time (MAT0–∞), 25.55 ± 15.27 h. These results suggest that PO administration of doxycycline could be useful as an antimicrobial drug in sheep.S

Effects of slowed gastrointestinal motility on levodopa pharmacokinetics

P. 67-72Autonomic disorders are often seen in Parkinson's disease, with disturbances of the gastrointestinal tract occurring most frequently. These disorders, mainly a delay in gastric emptying and slowed gastrointestinal motility, can modify the pharmacokinetics and effectiveness of drugs used to treat Parkinson's disease and administered orally. In this study, we evaluated in a rabbit model the pharmacokinetics of levodopa (administered with carbidopa) in the context of gastrointestinal motility slowed by the administration of an anticholinergic drug. Levodopa+carbidopa (20:5 mg/kg) and the anticholinergic biperiden (100 μg/kg) were orally administered to rabbits over one of two time periods (7 or 14 days) to verify the stabilization of levodopa concentrations. The values of the area under the curve (AUC) and Cmax were higher on the final day of treatment with an increase in AUC of 25% on day 7 and 33.4% on day 14; for Cmax, the increase was 15% on day 7 and 12.8% on day 14. The values of AUC and Cmax were lower than those obtained when levodopa was administered to rabbits with normal gastrointestinal motility. The values obtained for Cmin (baseline sample obtained before administration) also increased with treatment duration (24% and 47.4% on days 7 and 14, respectively). These values were higher than those obtained in the absence of anticholinergic administration. We conclude that, under our experimental conditions of slowed gastrointestinal motility, levodopa absorption diminishes, and final concentrations and Cmin are higher than under conditions of normal motility.S

Effects of Plantago ovata Husk on Levodopa (with Carbidopa) Bioavailability in Rabbits with Autonomic Gastrointestinal Disorders

P. 1434-1442Gastrointestinal dysfunction is common in Parkinson’s disease. Fiber therapy could be used to reduce the symptoms of gastrointestinal motility disorders. In a previous study, we showed that slowed gastrointestinal motility modified levodopa pharmacokinetics: area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) decreased and the elimination was delayed. In this study, we evaluated whether or not the hydrosoluble fiber Plantago ovata husk is useful in improving levodopa pharmacokinetics in rabbits with autonomic gastrointestinal disorders induced by the administration of the anticholinergic biperiden. Levodopa carbidopa (20:5 mg/kg), biperiden (100 g/ kg), and P. ovata husk (at two different doses: 100 and 400 mg/kg) were administered orally to rabbits for two periods of time (7 or 14 days). In all groups of animals, the AUC values were approximately 50% higher on the final day of treatment than on day 1. Cmax was also higher, with the greater increase at the 400 mg/kg dose of fiber, which resulted in a boost of approximately 35%. On day 1 of treatment and with both doses of fiber, AUC values were very similar to those obtained in previous work in rabbits with normal gastrointestinal motility, but the Cmax was lower. However, after 7 or 14 days, the AUC values were higher, but Cmax remained lower. The greatest differences were observed in plasma concentration before drug administration (Cmin), for which the highest increase was obtained with the dose of 400 mg/kg fiber on day 14 of treatment (349.8%). P. ovata husk could be beneficial in patients with Parkinson’s disease because it regulates stool transit in the intestine and because it improves levodopa pharmacokinetics when gastrointestinal peristalsis is slowed. These changes could lead to a possible delay in the onset of dyskinesias and to changes in prognosis.S

Desarrollo de simulador de negocios en la industria de sensores: estrategia y toma de decisiones

El objetivo del presente reporte académico es documentar las experiencias de aprendizaje que se vivieron durante el proceso de formulación, ejecución y evaluación de estrategias de negocios en un ambiente simulado altamente competitivo, así como evidenciar los resultados obtenidos por el equipo Ferris en la industria de sensores C70815 del simulador CAPSIM

VIVIR EN RÉGIMEN DE CONDOMINIO: CONFLICTOS VECINALES EN VIVIENDA DE INTERÉS SOCIAL, TIJUANA, BAJA CALIFORNIA.

En este trabajo se analizan los conflictos vecinales derivados del régimen de propiedad en condominio, bajo el cual se adquieren las viviendas de interés social promovidas por las instituciones del gobierno mexicano, así como por desarrolladores privados. Este régimen ha facilitado el acceso a la vivienda a la población asalariada, pero está lejos de contribuir a la consecución del derecho a la misma. La investigación toma como casos de estudio conjuntos habitacionales ubicados en la ciudad de Tijuana, Baja California, México. El análisis incluyó una metodología mixta. En primer lugar, se analizaron casos de estudio similares; en segundo lugar, se realizó la revisión de la Ley del Régimen de Propiedad en Condominio para conocer sus implicaciones. Ante la situación de pandemia, se aplicó una encuesta de manera virtual a los habitantes de estas zonas, así como entrevistas con presidentes de comités vecinales de estos conjuntos. A partir de lo anterior, se pudo constatar que esta forma de propiedad genera conflictos, reflejados en la insatisfacción de los habitantes con su vivienda, desacuerdos y controversias en su organización y convivencia. Los habitantes tienen que resolver de forma colectiva las problemáticas que enfrentan, relacionadas con el mantenimiento y uso de áreas comunes, inseguridad, limpieza, entre otros. Además, se observa la falta de apoyo de las autoridades locales. Con ello, se concluye que si bien los habitantes cuentan con un espacio que resuelve su problema de alojamiento, no logra ser un espacio que garantice adecuadamente su derecho a la vivienda