Pharmacokinetic parameters of (R)-(-) and (S)-(+)-flurbiprofen in dairy bovines.

The aim of the study was to evaluate the pharmacokinetics of flurbiprofen (FBP) in different age groups and physiological status groups in dairy cattle. Ten Argentine Holstein bovines were divided into three different groups: 3 cows in early lactation, 3 cows in gestation and 4 newborn calves. Based on previous experience, all the animals received racemic FBP (50:50) at a dose of 0.5 mg/kg by intravenous administration. Blood samples were taken at predetermined times after administration of flurbiprofen. Plasma enantiomer concentrations were measured by HPLC. Total body clearance (ClB) of (S)-(+)-FBP was higher in calves than in cows (114.5, 136.4, 121.4, 128.9 microg/ml vs 22.0, 24.2, 46.5 microg/ml and 27.6, 25.3, 34.6 microg/ml). In calves the disposition kinetics showed stereoselective behaviour. Area under the concentration-time curve (AUC) was higher and Cl(B) and steady-state volume of distribution (V(ss)) were lower for (R)-(-)-FBP than for (S)-(+)-FBP. In cows, stereoselectivity was observed in Cl(B) and elimination half-life (t(1)/2) only in the early lactation group. In this study, enantioselective metabolic behaviour of FBP under the physiological situations studied was found. Hence, it is possible that both enantiomers of flurbiprofen may contribute to the drug's therapeutic effects, but further studies with the administration of separate enantiomers will be required to elucidate their metabolism.

Some pharmacokinetic parameters of R-(-)- and S-(+)-ketoprofen: the influence of age and differing physiological status in dairy cattle.

The pharmacokinetic parameters of ketoprofen have previously been studied in cattle, but no studies have been performed on differing ages and metabolic situations in these animals. The aim of this work was to study the possible modifictions of the pharmacokinetics of ketoprofen enantiomers that may result from age, lactation or gestation in dairy cattle. Three groups of Holando Argentino cattle contained, respectively, 8 cows in early lactation, 8 pregnant cows and 8 newborn calves. Four animals from each group received the enantiomer R-(-)-ketoprofen, the other four animals received the S-(+) enantiomer, all by intravenous injection at a dose of 0.5 mg/kg. Significant differences between the three categories of animals were obtained in elimination half-life (t1/2) (1.52, 0.87 and 0.31 and 1.71, 0.69 and 0.26 in newborn calves, cows in early lactation and cows in gestation, respectively), mean residence time (MRT) (0.45, 1.25, 2.20 and 0.38, 0.99, 2.47 h, in cows in gestation, cows in early lactation and newborn calves, respectively) and area under the plasma concentration-time curve (AUC) (0.87, 2.93, 3.24, and 0.67, 2.78, 5.13 (microg/h)/ml in cows in gestation, cows in early lactation and newborn calves, respectively, for the R-(-) and S-(+) enantiomer, respectively. In calves, there was a significant difference in AUC (3.24 vs 5.13 (microg/h)/ml between R-(-)- and S-(+)-ketoprofen. In view of the differences between calves and adult cattle in the pharmacokinetic results for ketoprofen, the effects of age and physiological status (lactation, gestation) should be taken into account for therapeutic regimens.

Chiral inversion of (R)-ketoprofen: influence of age and differing physiological status in dairy cattle.

The chiral inversion of ketoprofen has been previously demonstrated in cattle, but no studies have been performed on different ages and metabolic situations in the animals. The aim of this work was to study any modifications of the stereoconversion of ketoprofen that occur by reason of age, lactation or gestation in dairy cows. Holando Argentino cattle were divided into three groups: 8 cows in early lactation, 8 pregnant cows and 8 newborn calves. Four animals from each group received the enantiomer R-(-)-ketoprofen by intravenous administration; the other four animals received the S-(+) enantiomer, all at doses of 0.5 mg/kg. Blood samples were collected at standardized times after dosing and assayed for ketoprofen by high-performance reversed-phase liquid chromatography (HPLC). The percentage inversion of R-(-)-ketoprofen to S-(+)-ketoprofen was 50.5% (SD +/- 2.4) in the preruminants, 33.3% (SD +/- 1.7) in cows in early lactation and 26.0% (SD +/- 5.1) in cows in gestation. These results indicate a differing enantioselective metabolic behaviour for one compound in one species under different physiological situations.

[Experimental model for the study of molybdenosis in the primary copper deficiency in rats]. / Modelo experimental para el estudio de la molibdenosis y de la deficiencia primaria de cobre en ratas.

An experimental model in rats was evaluated to differentiate the effects between Copper deficiency and Molybdenosis. Sixty weaning rats (30 male and 30 female) received a diet with 70% complete powder milk (1 ppm Cu) and 30% maize meal (0.8-1.5 ppm Cu). Three experimental groups received the following mineral supplementation: copper deficiency (40 ppm Fe), molybdenosis (40 ppm Fe + 40 ppm Cu + 500 ppm Mo) and control (40 ppm Fe + 40 ppm Cu). The animals were weighed each 14 days. At 70 days of treatment were sacrificed. Blood and liver were sampled for analyzing hematocrit, ceruloplasmin activity and Cu and Mo liver concentration. Copper deficiency group had less serum ceruloplasmin activity. Cu and Mo liver concentration were higher in the animals with molybdenosis. We concluded that when Cu levels are higher than minimum requirement, feeding with high Mo, do not affect ceruloplasmin activity. In addition, high Mo liver concentration allows us to elucidate effects "per se" of molybdenosis.

Modelo experimental para el estudio de la molibdenosis y de la deficiencia primaria de cobre en ratas / Experimental model for the study of molybdenosis in the primary copper deficiency in rats

Con el objetivo de diferenciar los efectos producidos por la deficiencia primaria cobre y los provocados por el excesso de molibdeno se evaluó un modelo experimental en ratas. Sesenta ratas de destete (30 machos y 30 hembras) recibieron una dieta compuesta por 70 por ciento de leche entera en polvo (1 ppm Cu) y 30 por ciento de harina de maíz (0.8 - 1.5 ppm Cu). Los animales se dividieron en tres grupos conforme a la suplementación mineral recibida: deficiencia primaria de cobre (40 ppm Fe), molibdenosis (40 ppm Fe + 40 ppm Cu + 500 ppm Mo) y controles (40 ppm Fe + 40 ppm Cu). Se pesaron cada 14 días. Al cabo de 70 días de tratamiento se obtuvieron muestras de sangre para determinación de hematocrito y actividad sérica de ceruloplasmina y se sacrificaron para medir concentraciones hepáticas de Cu y Mo. El grupo deficiente en Cu tuvo valores significativamente inferiores en la actividad de ceruloplasmina. Las concentraciones hepáticas de Cu y Mo fueron superiores significativamente en los animales con molibdenosis. Se concluye que con niveles de Cu por encima de los requerimientos mínimos, la alimentación con alto contenido de Mo, no afecta la actividad sérica de ceruloplasmina. Esto sumado a la concentración hepática de Mo lograda, permitirá identificar efectos "per se" de la molibdenosis. (AU)

Modelo experimental para el estudio de la molibdenosis y de la deficiencia primaria de cobre en ratas / Experimental model for the study of molybdenosis in the primary copper deficiency in rats

Con el objetivo de diferenciar los efectos producidos por la deficiencia primaria cobre y los provocados por el excesso de molibdeno se evaluó un modelo experimental en ratas. Sesenta ratas de destete (30 machos y 30 hembras) recibieron una dieta compuesta por 70 por ciento de leche entera en polvo (1 ppm Cu) y 30 por ciento de harina de maíz (0.8 - 1.5 ppm Cu). Los animales se dividieron en tres grupos conforme a la suplementación mineral recibida: deficiencia primaria de cobre (40 ppm Fe), molibdenosis (40 ppm Fe + 40 ppm Cu + 500 ppm Mo) y controles (40 ppm Fe + 40 ppm Cu). Se pesaron cada 14 días. Al cabo de 70 días de tratamiento se obtuvieron muestras de sangre para determinación de hematocrito y actividad sérica de ceruloplasmina y se sacrificaron para medir concentraciones hepáticas de Cu y Mo. El grupo deficiente en Cu tuvo valores significativamente inferiores en la actividad de ceruloplasmina. Las concentraciones hepáticas de Cu y Mo fueron superiores significativamente en los animales con molibdenosis. Se concluye que con niveles de Cu por encima de los requerimientos mínimos, la alimentación con alto contenido de Mo, no afecta la actividad sérica de ceruloplasmina. Esto sumado a la concentración hepática de Mo lograda, permitirá identificar efectos "per se" de la molibdenosis.

Modelo experimental para el estudio de la molibdenosis y de la deficiencia primaria de cobre en ratas. / [Experimental model for the study of molybdenosis in the primary copper deficiency in rats]

An experimental model in rats was evaluated to differentiate the effects between Copper deficiency and Molybdenosis. Sixty weaning rats (30 male and 30 female) received a diet with 70

complete powder milk (1 ppm Cu) and 30

maize meal (0.8-1.5 ppm Cu). Three experimental groups received the following mineral supplementation: copper deficiency (40 ppm Fe), molybdenosis (40 ppm Fe + 40 ppm Cu + 500 ppm Mo) and control (40 ppm Fe + 40 ppm Cu). The animals were weighed each 14 days. At 70 days of treatment were sacrificed. Blood and liver were sampled for analyzing hematocrit, ceruloplasmin activity and Cu and Mo liver concentration. Copper deficiency group had less serum ceruloplasmin activity. Cu and Mo liver concentration were higher in the animals with molybdenosis. We concluded that when Cu levels are higher than minimum requirement, feeding with high Mo, do not affect ceruloplasmin activity. In addition, high Mo liver concentration allows us to elucidate effects [quot ]per se[quot ] of molybdenosis.