C. Palma

Plasma disposition and fecal elimination of doramectin after oral or intramuscular administration in horses

A study was done to compare plasma disposition kinetics and the fecal elimination profile of doramectin (DRM) after oral or intramuscular (IM) administration in horses. Ten clinically healthy horses, 328-502 kg body weight (bw), were assigned to 2 experimental groups of 5 horses each. Group 1 was treated with an oral dose of 0.2 mg DRM/kg bw, while Group 2 was treated with 0.2 mg DRM/kg bw by IM route. Blood and fecal samples were collected at different times between 0.5h and 60 days post-treatment. After plasma and fecal drug extraction and derivatization, samples were analysed by high performance liquid chromatography (HPLC). A non-compartmental kinetic analysis was performed. Results were expressed as mean+/-standard deviation and were compared using Mann-Whitney U-test. The parent molecule was detected in plasma between 30 min and either 30 (oral) or 60 (IM) days post-treatment. Peak plasma concentrations (C(max)) of 51.6+/-22.2 and 33.3+/-10.5 ng/mL were obtained after oral administration and IM route, respectively. Differences between administration route were not statistically significant (P=0.42). The value for the area under the concentration-time curve (AUC) was 178.6+/-53.7 and 393.6+/-66.6 ng day/mL for Group 1 and Group 2, respectively. These differences were significant (P<0.0079). The averages for mean residence time (MRT) values were 7.7+/-0.9 and 13.2+/-4.5 days for oral and IM treated groups, respectively. In horses treated using the oral route, the peak fecal concentration (F C max) was 2295+/-593 ng/g observed at 1.9+/-0.5 days after oral treatment. Whereas, for those treated by IM route, the F C max was lower (162+/-26 ng/g) (P<0.0079) and it was observed at 5.6+/-2.9 days. The results of this study showed that the administration route affects plasma disposition kinetics, bioavailability and fecal elimination of DRM.

Pharmacokinetics of florfenicol and florfenicol-amine after intravenous administration in sheep.

Florfenicol (FFC) is a broad spectrum antibacterial agent that is structurally related to chloramphenicol but differs from it by the presence of a para-methyl sulphonyl group instead of the p-nitro group and the presence of a fluorine atom instead of the hydroxyl group in the terminal primary alcohol function (EMEA, 2002). Their potency and broad spectrum of activity make FFC a good antibiotic for replacing chloramphenicol, which has been banned from use in food animals (Adams et al., 1987). Reports have shown that after administration FFC is partially transformed into FFC-amine (FFC-a), FF oxamic acid, monochloroFFC, and FFC alcohol in the bodies of animals. Although their ratios are different in different species, FFC-a is the largest of all of the metabolites, mostly in food animals (Li et al., 2006). Owing to that it is the longest-lived major metabolite in the liver of cattle, FFC-a is used as a marker residue for withdrawal calculations (EMEA, 1999). Thus, biotransformation is able to influence not only the safety and effectiveness of drugs, but also the pattern and the amount of residues that animal products intended for human consumption may eventually accumulate (Nebbia et al., 2003). The pharmacokinetics of FFC have been studied in different ruminant species such as cattle (Varma et al., 1986; Adams et al., 1987; Soback et al.,1995), sheep (Ali et al., 2003; Jianzhong et al., 2004; Lane et al., 2004), and goats (Atef et al., 2001). However, reports about the pharmacokinetics of its major metabolite FFC-a in animals are scarce, and at present, there are only limited references that describe its plasma disposition in rabbits (Park et al., 2007), chickens (Anadon et al., 2008), and dogs (Park et al., 2008). The therapeutic use of FFC in animals must be assessed not only in terms of its clinical efficacy but also considering the risk of presence of residues in edible tissues (Anadon et al., 2008). Actually, it seems that there is no available information about the metabolism of FFC and the plasmatic disposition of its main metabolite FFC-a, in sheep. Thus, in the current study, we quantified the plasma disposition of FFC-a, to estimate the level of metabolism of FFC in this animal species. For this purpose, we injected an intravenous bolus of FFC to adult clinically health sheep. This route of administration was selected to avoid any interference that could have the absorption phase on metabolism and disposition of FFC when the drug is administered by an extra-vascular route. The aim of this study was to evaluate the plasma disposition of FFC and its major metabolite FFC-a after a single intravenous administration in adult sheep. A group of six adult clinically healthy Suffolk Down sheep, 2.5 years old and 49.4 ± 6.4 kg in body weight (bw) were selected for this study. The sheep were housed in collective pens on a dry bed, fulfilling the individual requirements of space, ventilation, and free access to fresh water. The sheep were fed daily with alfalfa hay and supplemented with grain (400 g of barley per ewe) and water was provided ad libitum. The sheep had no previous exposure to any antibiotic and no drugs were given to the animals during acclimation or the study period. All procedures were performed with the authorization of the Ethical Committee for Animal Experimentation of the Faculty of Veterinary Sciences, Universidad de Concepcion, Chile. FFC 30% injectable solution (Nuflor ; Schering Plough, Kenilworth, NJ, USA) was administered as a single intravenous bolus at a dosage level of 20 mg ⁄kg bw to each animal. Blood samples (5 mL) were collected from the jugular vein before drug administration and at 0.05, 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, and 48.0 h after treatment. Samples were collected in heparinized tubes and then centrifuged at 1000 g to obtain the plasma, which was stored at )18 C. Animals were subjected to a visual inspection for any adverse effect for a period of 1 h after drug administration and then during each sampling time for a 48 h period. Florfenicol and FFC-a were extracted from the plasma by the method described by Li et al. (2006) and their concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC). The analytical standard FFC (99.4% J. vet. Pharmacol. Therap. 35, 508–511. doi: 10.1111/j.1365-2885.2011.01357.x. SHORT COMMUNICATION

Determinación de residuos de abamectina-triclabendazol en tejidos bovinos

SUMMARY Abamectin (ABM) and Triclabendazole (TCBZ) are two potent antiparasitic drugs that differ in their chemical structure and spectrum of action. In this study, a sensitive HPLC-method was developed and validated to determine ABM and TCBZ residues in bovine edible tissues, and the pattern of tissue depletion of an oral formulation containing the association abamectin (ABM) - triclabendazole (TCBZ) was characterized. Sixteen parasitefree heifers (232 ± 37.5 kg body weight) were treated with the oral formulation at a dose rate of 0.2 mg of ABM/kg and 10mg of TCBZ/kg of live weight. Treated animals were slaughtered weekly in randomly selected groups of three to four animals from day 7 until day 42 post-treatment. Concentration profiles of the drugs were determined in liver, kidney, muscle and fat tissues. Two nontreated animals were slaughtered in order to obtain blank tissue samples to validate the analytical methodology. Drug concentration profiles were determined by a validated HPLC analytical methodology using fluorescence detection for ABM and UV- detection for TCBZ. The highest concentration of ABM was observed in liver samples (4.02 ng/g) and was maintained for 14 days. In the case of TCBZSO 2 the highest concentration was observed in the kidney (0.79 μg/g) and persisted for a period of 14 days.

Pharmacokinetics of ivermectin after maternal or fetal intravenous administration in sheep

In pregnant sheep at 120-130 days of gestational age, a study was undertaken in order to characterize the pharmacokinetics and transplacental exchange of Ivermectin after maternal or fetal intravenous administration. Eight pregnant Suffolk Down sheep of 73.2 +/- 3.7 kg body weight (bw) were surgically prepared in order to insert polyvinyl catheters in the fetal femoral artery and vein and amniotic sac. Following 48 h of recovery, the ewes were randomly assigned to two experimental groups. In group 1, (maternal injection) five ewes were treated with an intravenous bolus of 0.2 mg ivermectin/kg bw. In group 2, (fetal injection) three ewes were injected with an intravenous bolus of 1 mg of ivermectin to the fetus through a fetal femoral vein catheter. Maternal and fetal blood and amniotic fluid samples were taken before and after ivermectin administration for a period of 144 h post-treatment. Samples were analyzed by liquid chromatography (HPLC). A computerized non-compartmental pharmacokinetic analysis was performed and the results were compared by means of the Student t-test. The main pharmacokinetic changes observed in the maternal compartment were increases in the volume of distribution and in the half-life of elimination (t((1/2)beta)). A limited maternal-fetal transfer of ivermectin was evidenced by a low fetal Cmax (1.72 +/- 0.6 ng/mL) and AUC (89.1 +/- 11.4 ng.h/mL). While the fetal administration of ivermectin resulted in higher values of clearance (554.1 +/- 177.9 mL/kg) and lower values of t((1/2)beta) (8.0 +/- 1.4 h) and mean residence time (8.0 +/- 2.9 h) indicating that fetal-placental unit is highly efficient in eliminating the drug as well as limiting the transfer of ivermectin from the maternal to fetal compartment.

Pharmacokinetics of ivermectin in pregnant and nonpregnant sheep

The plasma kinetic profile of ivermectin during the last trimester of pregnancy was studied in ewes after a single subcutaneous administration of 0.2 mg/kg body weight (BW). Sheep were randomly distributed into two groups. Ewes in group 1 (control, n=6) were left unmated, whereas in group 2 (pregnant, n=6) ewes were estrus-synchronized and mated with rams. Both groups were housed under similar conditions of management and feeding. At 120 days of pregnancy, both groups were given a subcutaneous injection of 0.2 mg/kg BW of ivermectin. Blood samples were taken by jugular puncture according to a fixed protocol between 1 h and 40 days post-treatment. After plasma extraction and derivatization, samples were analyzed by high performance liquid chromatography with fluorescence detection. A computerized pharmacokinetic analysis was performed, and the data were compared by means of the Student t-test. The results showed that plasma concentrations of ivermectin remained longer in the pregnant than in the control group. The mean values of pharmacokinetic parameters C(max), t(max), and area under the concentration-time curve (AUC) were similar for both groups of sheep. The mean residence time (MRT) values for the pregnant group (8.8+/-1.4 days) were higher (P<0.05) than those observed in the control group (5.3+/-1.9 days). It can be concluded that pregnancy increases the residence time of ivermectin in the plasma of pregnant sheep when it is administered subcutaneously.

Plasma and tissue disposition of florfenicol in Escherichia coli lipopolysaccharide-induced endotoxaemic sheep

Abstract 1. The purpose of this study was to understand the effects of the acute inflammatory response (AIR) induced by Escherichia coli lipopolysaccharide (LPS) on florfenicol (FFC) and FFC-amine (FFC-a) plasma and tissue concentrations. 2. Ten Suffolk Down sheep, 60.5 ± 4.7 kg, were distributed into two experimental groups: group 1 (LPS) treated with three intravenous doses of 1 μg/kg bw of LPS at 24, 16, and 0.75 h (45 min) before FFC treatment; group 2 (Control) was treated with saline solution (SS) in parallel to group 1. An IM dose of 20 mg FFC/kg was administered at 0.75 h after the last injection of LPS or SS. Blood and tissue samples were taken after FFC administration. 3. The plasma AUC0–4 h values of FFC were higher (p = 0.0313) in sheep treated with LPS (21.8 ± 2.0 μg·min/mL) compared with the control group (12.8 ± 2.3 μg·min/mL). Lipopolysaccharide injections increased FFC concentrations in kidneys, spleen, and brain. Low levels of plasma FFC-a were observed in control sheep (Cmax = 0.14 ± 0.01 μg/mL) with a metabolite ratio (MR) of 4.0 ± 0.87%. While in the LPS group, Cmax increased slightly (0.25 ± 0.01 μg/mL), and MR decreased to 2.8 ± 0.17%. 4. The changes observed in the plasma and tissue concentrations of FFC were attributed to the pathophysiological effects of LPS on renal hemodynamics that modified tissue distribution and reduced elimination of the drug.

Resistencia antihelmíntica en nematodos gastrointestinales de ovinos tratados con ivermectina y fenbendazol

Resumen es: Se realizo un estudio con el objetivo de evaluar la presencia de resistencia en nematodos gastrointestinales de ovinos tratados con los antihelminticos i...

The influence of gastrointestinal parasitism on fecal elimination of doramectin, in lambs.

A study was done to investigate the effect of parasitism on patterns of doramectin (DRM) fecal elimination in lambs. Fourteen Suffolk Down parasitized lambs (26.9 ± 1.5 kg body weight: bw) were purposely selected for the study. Seven pairs of lambs were allocated into two experimental groups. Group I (non-parasitized) was pre-treated with 3 repeated administrations of 5mg/kg bw of fenbendazole to maintain a non-parasitized condition. In Group II (parasitized), the lambs did not receive any anthelmintic treatment. After 85 d of the pre-treatment period, both groups were treated with a subcutaneous injection of 200 μg/kg bw of DRM. Fecal samples were collected at different times between -85 d before and 60 d after the DRM treatment, for both parasitological and chromatographic analysis. Samples were analyzed by high-performance liquid chromatography (HPLC) with fluorescence detection. Data of DRM concentrations were expressed as wet weight. A non-linear pharmacokinetic analysis was performed and results were compared using the Mann Whitney test. Fecal maximum concentrations (C(max)) of DRM were 1.37 ± 0.19 μg/g (parasitized group) and 0.86 ± 0.15 μg/g (non-parasitized group) observed at the time of the maximum concentration (T(max)) of 2.1 ± 0.4 and 3.1 ± 0.3d, respectively. Differences in C(max) values were significant (P<0.05). The accumulated elimination of DRM in feces, expressed as the percentage of DRM total dose, was 67.1% in the parasitized group, whereas in the non-parasitized group it was 56.5%. Our results showed that gastrointestinal parasitic diseases can modify the patterns of DRM fecal elimination, when the drug is administered by subcutaneous route in lambs.

Hematological and Biochemical Parameters of Captive Andean Condors

Abstract Hematological and biochemical parameters are used to assess the health of birds and to support conservation plans for threatened species, such as the Andean Condor (Vultur gryphus). We studied 22 captive Andean Condors from the Rehabilitation Center for Raptors of the Unión de Ornitólogos of Chile to determine reference values. We measured packed cell volume, total plasma solids, and total and differential leukocyte counts; we analyzed aspartate aminotransferase, gamma-glutamyl transpeptidase, lactate dehydrogenase, alkaline phosphatase, creatine kinase, creatinine, calcium, inorganic phosphorus, and uric acid. We found no blood parasites and no significant differences between sexes (P > 0.05). Our results establish a baseline for hematological and serum biochemistry parameters for the Andean Condor.

Haematological and blood biochemical changes induced by the administration of low doses of Escherichia coli lipopolysaccharide in rabbits

El objetivo fue investigar los cambios hematologicos y en la bioquimica sanguinea inducidos por la administracion de dosis bajas de lipopolisacarido de Escherichia coli (LPS) en conejos. Seis conejos clinicamente sanos fueron distribuidos en dos grupos experimentales mediante un diseno cruzado: Grupo 1 (LPS) tratado con dos dosis intravenosas de 1 μg/kg de LPS. Grupo 2 (Control) fue tratado con un volumen equivalente de solucion salina (SS). Previo y posterior a la administracion de LPS se midio temperatura rectal (°C), se determinaron las concentraciones de interleukina 6 (IL-6), proteina C reactiva (PCR), ademas se realizo hemograma y se midio la actividad de las enzimas aspartato aminotransferasa (AST) y gamma glutamil transferasa (GGT). La administracion de LPS produjo aumentos significativos en la temperatura rectal, IL-6 y PCR. A las 4 y 8 h posteriores a la inyeccion de LPS se observo leucopenia asociada a disminucion en el recuento de monocitos, linfocitos y plaquetas, mientras que a las 12 y 24 h el recuento de leucocitos y neutrofilos aumento significativamente. No se observaron cambios en los promedios de VGA, concentracion de proteinas totales y albumina o en la actividad de las enzimas AST y GGT. Se concluye que las modificaciones hematologicas y de bioquimica sanguinea inducidas por la administracion de dosis bajas de LPS son de moderada intensidad y corta duracion en comparacion a las descritas en conejos tratados con dosis altas de LPS. Estos cambios son consistentes con un estado de respuesta inflamatoria inicial inducida por una infeccion por Gram negativos