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

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

Sex-Specific Effects of Early Life Stress on Brain Mitochondrial Function, Monoamine Levels and Neuroinflammation

Sex differences have been reported in the susceptibility to early life stress and its neurobiological correlates in humans and experimental animals. However, most of the current research with animal models of early stress has been performed mainly in males. In the present study, prolonged maternal separation (MS) paradigm was applied as an animal model to resemble the effects of adverse early experiences in male and female rats. Regional brain mitochondrial function, monoaminergic activity, and neuroinflammation were evaluated as adults. Mitochondrial energy metabolism was greatly decreased in MS females as compared with MS males in the prefrontal cortex, dorsal hippocampus, and the nucleus accumbens shell. In addition, MS males had lower serotonin levels and increased serotonin turnover in the prefrontal cortex and the hippocampus. However, MS females showed increased dopamine turnover in the prefrontal cortex and increased norepinephrine turnover in the striatum, but decreased dopamine turnover in the hippocampus. Sex differences were also found for pro-inflammatory cytokine levels, with increased levels of TNF-α and IL-6 in the prefrontal cortex and hippocampus of MS males, and increased IL-6 levels in the striatum of MS females. These results evidence the complex sex- and brain region-specific long-term consequences of early life stress.This work was supported by grants PSI 2017-83038-P to HGP and NC, PSI 2017-90806-REDT to JLA, PSI 2017-83893-R to JLA (Ministry of Economy and Competitiveness, Spain)

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

Effect of glucomannan and the dosage form on ethinylestradiol oral absorption in rabbits

P. 423-427To the beneficial properties of dietary fiber in human health, several disadvantages can be added as the possible modification of the bioavailability of other drugs when administered by the oral route. In this study, the influence of glucomannan in the oral bioavailability of ethinyl estradiol (EE), when administered to female rabbits in two different dosage forms (enteric capsules and dispersed in water), was established. To carry out the study, three groups of six animals each were used. All animals received 1 mg kg 1 oral EE, and rabbits in groups 2 and 3 received 1.5 g glucomannan dispersed in water or in enteric capsules, respectively, immediately before EE. When comparing the results obtained after the administration of EE/glucomannan dispersed in water with those obtained after the administration of this estrogen without fiber, we can see that Cmax is 1.4 times lower, AUC 1.9 times lower and that tmax is identical (10 min). However, after the administration of fiber in enteric capsules, AUC and Cmax are higher (4.1 and 7.8 times, respectively) than when the estrogen was administered alone, and also, there is a delay in tmax (20 min). After the administration of glucomannan in the enteric capsule, the fiber forms, as in the stomach, a highly viscous solution in the gut that would limit EE access to the mucosal surface delaying its absorption. However, this effect could be compensated by a reduction of EE metabolism in the intestinal wall, leading to a higher absorption of the estrogen.S

IAPT chromosome data 28

[EN] Veronica angustifolia (Vahl) Bernh.; Veronica austriaca subsp. jacquinii (Baumg.) Watzl; Veronica dalmatica N.Pad.Gar., Rojas-Andrés, López-González & M.M.Mart.Ort.; Veronica kindlii Adam.; Veronica orsiniana Ten.; Veronica prostrata L.; Veronica rosea Desf.; Veronica sennenii (Pau) M.M.Mart.Ort. & E.Rico; Veronica tenuifolia subsp. javalambrensis (Pau) Molero & J.Pujadas; Veronic tenuifolia Asso subsp. tenuifolia; Veronica teucrium L.; Veronica thracica Velen.. In: K. Marhold & J. Kucera, IAPT chromosome data 28

Documentar gráficamente para la memoria

In the field of Heritage and its conservation, drawing accentuates the communicational value that is its own. The graphic documentation is a useful tool for the preservation of cultural values. It represents the architectural good in its entirety, and in the future, it can become a historical document, a graphic testimony of the culture that generates it. San Juan, is a province hit by earthquakes periodically; therefore we need the heritage graphical documentation to assure the transmission of the cultural legacy to the future.Las reflexiones vertidas en este trabajo están basadas en el Proyecto de Investigación desarrollado en el Instituto Regional de Planeamiento y Hábitat (IRPHA) de la FAUD, UNSJ denominado "Modelo de documentación gráfica para el registro de un bien patrimonial en una zona sísmica". En el campo del Patrimonio y su conservación, el dibujo acentúa el valor comunicacional que le es propio. La documentación gráfica constituye una herramienta útil para la preservación de los valores culturales. Representa el bien arquitectónico en su totalidad y a futuro puede convertirse en documento histórico, testimonio gráfico de la cultura que lo genera San Juan es una provincia de características árida sísmica donde surge la necesidad de entender y reafirmar los objetos patrimoniales existentes como recursos no renovables, ya que periódicamente se pierde lo tangibll. En 1944 un terremoto tuvo efectos desastrosos sobre la edificación de la ciudad de San Juan, llegando a ser un hito que distinguió al patrimonio en pre 44 o post 44. Atendiendo a esto, la documentación gráfica del patrimonio adquiere, entonces, "valor documental" y contribuye así, a la preservación de nuestra identidad y memoria. El objeto de estudio seleccionado fue el conjunto de la Capilla de la Parroquia Sagrada Familia del departamento Zonda. El trabajo consideró fundamental, la incorporación de diferentes técnicas gráficas analógicas y digitales como modo de registro, ya que cada una de ellas conlleva una mirada y un modo particular de narrar el espacio patrimonial.Facultad de Arquitectura y Urbanism

Hydrosoluble fiber (Plantago ovata husk) and levodopa I: Experimental study of the pharmacokinetic interaction

P. 497.503Fiber therapy could be used in patients with Parkinson disease to reduce the symptoms of gastrointestinal disorders; however, it could interact with levodopa reducing its effectiveness. In this experimental study we have investigated whether the presence of Plantago ovata husk (water-soluble fiber) modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route at the same time. We have also studied whether pharmacokinetic modifications are fiber–dose dependent (100 and 400 mg/kg). The extent of levodopa absorbed when administering 100 mg/kg of fiber (AUC=43.4 Ag min ml 1) is approximately the same as when levodopa is administered alone (AUC=47.1 Ag min ml 1); however, Cmax is lower (1.04 versus 1.43 Ag ml 1). Results obtained indicate that fiber at the higher dose increases the extent of levodopa absorbed (AUC=62.2 Ag min ml 1), being the value of Cmax similar (1.46 Ag ml 1). The value of tmax increases from 10 min when levodopa is administered alone to 20 min when the animals receive fiber. On the other hand, since certain time on, levodopa concentrations are always higher in the groups that receive fiber: 60 min with 100 mg/kg fiber and 20 min with 400 mg/kg fiber. Fiber also increases the mean residence time (MRT). P. ovata husk administration with levodopa could be beneficial, not only in patients with constipation, due to: lower adverse reactions (lower values of Cmax) and longer and more stable effects (higher final concentrations and more time in the body).S

Hydrosoluble fiber (Plantago ovata husk) and levodopa II: Experimental study of the pharmacokinetic interaction in the presence of carbidopa

P. 505-509Levodopa combined with carbidopa constitutes one of the most frequent medication in the treatment of Parkinson’s disease. Plantago ovata husk (water-soluble fiber) improves levodopa absorption conditions, but when this drug is administered with carbidopa, fiber could reduce its effectiveness. The purpose of this study is to investigate whether the presence of P. ovata husk modifies in rabbits the bioavailability and other pharmacokinetic parameters of levodopa (20 mg/kg) when administered by the oral route with carbidopa (5 mg/ kg). We have also studied whether pharmacokinetic modifications are fiber–dose dependent (100 and 400 mg/kg). When levodopa and carbidopa were administered with 100 mg/kg P. ovata husk, the value of AUC for levodopa diminishes 29.7% (sign, n =6, P b0.05) and Cmax 28.1% (sign, n =6, P b0.05) in relation to the values obtained when these drugs were administered without fiber. If the dose of fiber was 400 mg/kg, the decrease was smaller: 20.4% for AUC (no significant difference) and 24.6% for Cmax (sign, n =6, P b0.05), that may indicate an inhibitory action of AADC by the fiber or any of its partial hydrolysis products. On the other hand, since certain time on, levodopa concentrations are always higher in the groups that receive fiber: 210 min with 100 mg/kg and 150 min with 400 mg/kg. The administration of P. ovata husk with levodopa/carbidopa to patients with Parkinson disease could be beneficial and in particular in those patients who also suffer constipation due to an improvement of levodopa kinetic profile with higher final concentrations, a longer plasma half-life and lower Cmax.S