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

El sistema català de recerca i innovació en el context europeu: avaluació i reptes

La política científica forma part de l’eix de les polítiques socioeconòmiques als estats europeus més avançats, per aquesta raó la Unió Europea ha promogut les Research Innovation Strategies for Smart Specialisation-RIS3, amb la intenció que els estats i les regions prioritzin la seva activitat econòmica sobre la base dels seus avantatges competitius i la seva massa crítica. En aquest context, moltes regions europees han pres consciència del potencial de les seves polítiques científiques, entre les quals destaca Catalunya. Aquesta regió ha desenvolupat des de fa dècades de manera intensa la seva competència en recerca i innovació, per la qual cosa resulta fonamental detectar quins són els seus reptes de futur en aquest àmbit. Amb aquesta finalitat, el present article ha seleccionat una sèrie de models de dret comparat i un conjunt de temes per avaluar, per tal d’identificar mancances i proposar reformes en el sistema català. Concretament, els països de referència han estat Alemanya, Àustria i el Regne Unit, i els temes la gestió/governança de la ciència i la planificació científica, incloent-hi en ambdós casos la qüestió de la col·laboració publicoprivada i la transferència de coneixements i resultats

Hypoglycemic and hypolipidemic potential of a high fiber diet in healthy versus diabetic rabbits

P. 960568 - 960575The aim of this study was to investigate potential hypoglycaemic and hypolipidemic effects of Plantago ovata husk included in the diet, in healthy and diabetic rabbits. We also examined the effects of this fiber in other biochemical parameters. Two groups of 18 rabbits were used.The first group was fed with standard chow and the second with chow supplemented with Plantago ovata husk (3.5mg/kg/day). On day 14 diabetes mellitus was induced by the intravenous administration of alloxan (80mg/kg). After an oral glucose load (3 g), glucose, insulin, and other biochemical parameters were determined on day 14 (healthy rabbits) and on day 28 (diabetic rabbits). In healthy rabbits, fiber did not modify glucose or insulin levels but decreased significantly total cholesterol, LDL-cholesterol, atherogenic index, and glycosylated hemoglobin. In diabetic rabbits, fiber was more beneficial in mild diabetics than in severe diabetics with significant decreases in glucose levels and increases in insulin concentrations. In these animals fiber caused an important reduction in cholesterol, indicating a beneficial effect of Plantago ovata husk in diabetic rabbits. Although further studies in patients are necessary, we think that Plantago ovata husk offers interesting perspectives to be administered to patients with diabetes mellitus.S

Fatigue Study of the Pre-Corroded 6082-T6 Aluminum Alloy in Saline Atmosphere

[Abstract] This work studies the influence of the saline atmospheric corrosion on the fatigue strength of 6061-T6 aluminum alloy. For this purpose, this alloy was subjected to tests in a salt spray corrosion chamber at different exposure times (1, 2, and 3 months) according to ASTM B117 standard. The morphological study of the pits was carried out by confocal microscopy. Subsequently, fatigue tests were performed at variable stresses whose maximum stress (Smax) was between 30% and 95% of the yield strength (S0) in order to keep them within the zone of elastic behavior of the material. Data were analyzed using the Basquin equation and the maximum likelihood function method. The results show a similar decrease in the conventional fatigue limit (2 × 106 cycles) after one month (98 MPa) and two months (91 MPa) of corrosion. After three months of corrosion, the material showed a very important reduction in the fatigue limit (68 MPa) with respect to the uncorroded material (131 MPa). The data of Se/S0 (fatigue limit/yield strength) versus the ratio Pm/Dm (pit average depth/pit diameter at zero depth) can be fitted to a logarithmic curve

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

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

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