Effect of condensed tannin ingestion in sheep and goat parotid saliva proteome

Saliva appears as a defence mechanism, against potential negative effects of tannins, in some species of animals which have to deal with these plant secondary metabolites in their regular diets. This study was carried out to investigate changes in parotid saliva protein profiles of sheep (Ovis aries) and goats (Capra hircus), induced by condensed tannin ingestion. Five Merino sheep and five Serpentina goats were maintained on a quebracho tannin enriched diet for 10 days. Saliva was collected through catheters inserted on parotid ducts and salivary proteins were separated by two-dimensional gel electrophoresis. Matrix-assisted Laser desorption ionization - time of flight (MALDI-TOF) and liquid chromatography tandem mass spectrometry (LC-MS/MS) were used to identify the proteins whose expression levels changed after tannin consumption. Although no new proteins appeared, quebracho tannin consumption increased saliva total protein concentration and produced changes in the proteome of both species. While some proteins were similarly altered in both species parotid salivary protein profile, sheep and goats also presented species-specific differences in response to tannin consumption.     

Gamithromycin plasma and skin pharmacokinetics in sheep

This study assessed the plasma kinetics and skin/plasma concentration ratio of the azalide antibiotic gamithromycin (ZACTRAN^®, Merial) in sheep after a single subcutaneous administration at 6 mg/kg bodyweight. Gamithromycin concentrations in plasma samples collected at various intervals up to 21 days following treatment and metacarpal skin obtained from animals at two, five and ten days after treatment were determined by liquid chromatography–tandem mass spectrometry methods.     

The pharmacokinetics of chloramphenicol in plasma and saliva of dairy cows

In the present study the pharmacokinetics of chloramphenicol were investigated in bovine plasma and saliva. The method of detection of chloramphenicol, a radio-immunoassay, requires only small sample volumes, no further clean-up, and a large number of samples can be processed simultaneously. This enabled the collection of a larger number of samples over a longer period of time than in previous studies. The intention was to obtain a complete pharmacokinetic profile of chloramphenicol, to evaluate it according to common open-compartment models, and to compare it with the results of previous studies. The radio-immunoassay results were confirmed by analysing a number of samples distributed over the concentration range of interest by a gas-chromatographic method with electron-capture detection. The suitability of saliva was evaluated as a possible means of monitoring compliance with the ban on chloramphenicol in the Federal Republic of Germany in milk-producing animals.     

Comparative pharmacokinetics of amikacin sulphate in calves and sheep

The pharmacokinetics of amikacin sulphate were investigated in calves and sheep. Five animals of each species were given 7.5 mg kg-1 intravenously and intramuscularly. After intravenous administration the pharmacokinetic parameters significantly different (P less than 0.01) between calves (first value) and sheep (second value), were: the initial concentration (87.05, 146.6 micrograms ml-1), the apparent distribution volume (350, 200 ml kg-1), the area under curve (5512, 11,018 min micrograms ml-1) and the clearance (1.5, 0.7 ml min-1 kg-1). After dosing intramuscularly the peak concentration (23.5, 34.36 micrograms ml-1), the peak time (45, 75 min) and the area under curve (5458, 9191 min micrograms ml-1) were significantly different (P less than 0.01). No significant differences were observed in the terminal halflife values, suggesting that elimination rate was independent of both route of administration and animal species. The drug in aqueous solution showed a good bioavailability in both animal species (about 0.87 in sheep and greater than 0.99 in calves) despite the greater serum concentrations always attained in sheep.     

Comparative pharmacokinetics of triclabendazole in camels and sheep]

The authors describe the compared pharmacokinetics of triclabendazole in three camels and four sheep which were given orally a single dose of 10 mg/kg liveweight. Plasma concentrations of triclabendazole and its main metabolites were determined by high performance liquid chromatography. No parental drug was detected in the blood plasma due to a hepatic first passage effect. It appeared that there was a major difference between the two species, triclabendazole sulfoxide concentrations being two times lower in camels than in sheep.     

Comparative pharmacokinetics of ampicillin-sulbactam combination in calves and sheep

The pharmacokinetics of ampicillin and sulbactam administered in combination were studied in calves and sheep. The animals were administered an aqueous solution of ampicillin/sulbactam (2: 1, w/w) intravenously and intramuscularly at doses of 13.2 and 6.6 mg.kg^-1, respectively. A microbiological method was used to detect ampicillin, and HPLC was used to detect sulbactam in serum. Following intravenous (i, v.) administration, the distribution phases were rapid and similar (about 15 min) for both drugs in both species, whereas sulbactam in calves and ampicillin in sheep showed a faster elimination rate. After intramuscular (i.m.) administration both drugs showed peak concentrations higher in calves than in sheep: the peak time of sulbactam was shorter in calves than in sheep. No other significant differences in the pharmacokinetics of the combination were observed between the species after i.m. injection. The mean residence and absorption times, calculated by non-compartmental analysis, for both calves and sheep suggested that the differences in ampicillin and sulbactam phgrmacokinetics could be attributable to the different molecular structures.     

Comparative pharmacokinetics of diminazene in lactating goats and sheep

The pharmacokinetic aspects of diminazene aceturate were studied in lactating goats and sheep after single intravenous and intramuscular administrations of 3.5 mg/kg b.wt. Plasma and milk concentrations were determined by use of reversed phase high-performance liquid chromatography (HPLC) after ion-pair extraction. Following intravenous injection, the disposition of diminazene in goats and sheep conformed to a two-compartment model with rapid distribution and slower elimination phases. Values of (t1/2 beta) were obtained indicating a slower final disappearance of the drug from plasma of sheep (21.17 h) than in goats (16.39 h). Diminazene concentrations were maintained for more than 4 days in the plasma of goats and sheep. In both species of animals, diminazene was rapidly absorbed following intramuscular administration of 3.5 mg/kg b.wt. The peak plasma concentrations (Cmax) were 7.00 and 8.11 micrograms/ml and were attained at (Tmax) 0.92 and 1.12 hours in goats and sheep, respectively. The elimination half-life (t1/2el) of diminazene after intramuscular administration was shorter in goats (16.54 h) than in sheep (18.80 h). Systemic bioavailabilities (F%) of diminazene after intramuscular administration were 94.94% and 82.64% in goats and sheep, respectively. Diminazene could be detected in milk of goats and sheep within 10 min post-injection. Milk concentrations of the drug were lower in goats than in sheep and were detected for 5 and 6 days following both routes of administration, respectively.     

Bioavailability and pharmacokinetics of sulfamethazine in the pony

Sulfamethazine has been used in therapy of equine disease for over 40 years (Welsh et al , 1946). Although sulfamethazine appears to be well absorbed when fed mixed with grain and is reported to reach its peak concentration 8 h after administration, its oral bioavailability and pharmacokinetics have not been reported (Schroeder et al. , 1948; Meier et al , 1980). The purpose of the present study was to determine the major pharmacokinetic values and the oral bioavailability of sulfamethazine at a dosage predicted to produce therapeutic blood concentrations in the pony.     

Comparative plasma kinetics of orally administered sulfamethazine in clinically parasitized and parasitism-treated lambs

Sulfamethazine was administered at a dosage of 99 mg/kg body weight to lambs with a naturally acquired parasitism and again at 37 days following treatment with an anthelmintic. Blood samples were analyzed for sulfonamides over a 72 h period following sulfamethazine administration in both phases of the study. Pharmacokinetic parameter estimates of the sulfonamide blood data demonstrated significantly lower peak levels, longer times to peak and higher blood levels of the drug as time after dosing increased, in the parasitized as compared with the parasitism-treated lambs.     

Comparative pharmacokinetics of febantel and its metabolites in sheep and cattle

The pharmacokinetics of febantel and its main metabolites were studied in cattle and sheep. Seven ewes and 4 heifers were given febantel orally in a single dose of 7.5 mg/kg, 25 mg/kg, or 45 mg/kg of body weight. Plasma concentrations vs time of febantel and individual metabolites were determined by high-performance liquid chromatography analysis. Intestinal absorption of febantel was faster and biotransformations were more active in sheep than in cattle.     

Comparative benzylpenicillin pharmacokinetics in the dromedary Camelus dromedarius and in sheep

Benzylpenicillin pharmacokinetics were compared in the dromedary Camelus dromedarius (n = 5) and in sheep (n = 5) after administration of a single intravenous injection of benzylpenicillin. The data were described by an open three-compartment model with elimination from the central compartment. Body clearance (Clb) was 4.87 +/- 0.63 ml/min/kg in the dromedary and 9.17 +/- 1.39 ml/min/kg in sheep, the steady-state volumes of distribution (Vss) were 0.151 +/- 0.023 l/kg and 0.165 +/- 0.038 l/kg and the mean residence times (MRT) 27.34 +/- 1.38 min and 14.95 +/- 4.16 min in the dromedary and in sheep, respectively. It was concluded that benzylpenicillin elimination occurs more slowly in the dromedary than in sheep and that use of the same dosage regimen for the two ruminant species may lead to significant differences in plasma concentrations and therapeutic efficacy.     

Comparative pharmacokinetics of amoxicillin administered intravenously to sheep and goats

The pharmacokinetic behavior of sodium amoxicillin was studied after intravenous administration to six sheep and five goats to determine if there are species differences in disposition. The plasma drug concentrations vs. time following intravenous administration of 10 mg/kg were best described by the biexponential equations Cp = 42.9e-0.077.t + 3.68e-0.0134.t for goats, and Cp = 53.5e-0.06.t + 1.69e-0.015.t for sheep. The terminal disposition half-lives for sheep and goats were 46.3 and 66.9 min respectively and were not significantly different. Amoxicillin clearance for sheep and goats were 10.1 and 11.4 ml/min.kg respectively. There were no significant differences between any of the pharmacokinetic parameters measured in sheep and goats.     

Pharmacokinetics, safety and tissue residues of sustained-release sulfamethazine in sheep

Concentration-time profiles and the rates of absorption, extent of distribution and half-lives of sulfamethazine (SMZ), administered intravenously, orally as a water solution and as a sustained-release formulation (CalfSpan) were determined in 10 healthy sheep. The geometric mean half-life of elimination of i.v. SMZ was 10.8 h, compared to 14.3 h for the sustained-release preparation (CalfSpan) and 4.3 h for the oral water solution. Blood levels of SMZ were at or above 50 micrograms/ml for more than 48 h for CalfSpan, for 24 h after i.v. SMZ (100 mg/kg body wt), and for less than 24 h after p.o. SMZ (100 mg/kg body wt). The mean bioavailability of the oral SMZ solution was 58.3% (AUCp.o./AUCi.v.). The estimated bioavailability of the CalfSpan preparation was 52.5%. The safety of the sustained-release preparation was tested by dosing sheep with multiples (one, three and five times) of the recommended dose (one tablet, 8 g SMZ, per 20 kg body wt), once a day for 3 days. Clinical blood chemistries showed a significant increase in serum iron, and a decrease in serum phosphorus in animals treated at the 3x and 5x dose levels. Necropsies of the 5x dose animals did not show any gross signs that could be attributed to SMZ, and histological examination of tissues from the 5x animals revealed no organ pathology. Residues of SMZ in liver, fat, kidney and skeletal muscle were measured in 20 animals that received one bolus per 20 kg body wt. The results indicate that SMZ residues are cleared rapidly, and are at or below the tolerance level of 0.1 mg/kg within 8 days after dosing so that the 18-day withdrawal time used in cattle would provide an appropriate margin of safety if used in sheep.     

Comparative pharmacokinetics of levamisole-oxyclozanide combination in sheep and goats following per os administration

Since there is no registered anthelmintic drug available for use in goats, extra-label use of drugs is a common practice in most countries. The aim of the present study was to compare the pharmacokinetic disposition of levamisole (LVM)-oxyclozanide (OXZ) combination in sheep and goats following per os administration. Goats (n = 8) and sheep (n = 8) 12- to 16-months-old were used for this study. The animals received tablet formulation of LVM and OXZ combination orally at a dose of 7.5 mg/kg and 15 mg/kg body weight, respectively. Blood samples were collected by jugular vein at different times between 5 min and 120 h after drug administrations. The plasma concentrations of LVM and OXZ were analyzed by HPLC following liquid-liquid phase extraction procedures. The plasma concentrations and systemic availabilities of both LVM and OXZ in goats were lower and the plasma persistence of LVM was shorter compared with those observed in sheep. Terminal half-lives (t_1/2λz) of both molecules are shorter in goats compared with those in sheep. Goats treated with LVM-OXZ combination at the recommended dose for sheep may result in a reduced efficacy, because of under-dosing, which may increase the risk of drug resistance in parasites. Increased or repeated dose could be a strategy to provide higher plasma concentration and thus to improve the efficacy against the target parasites in goats compared with sheep. However, some adverse reactions may occur since LVM has relatively very narrow therapeutic index due to its nicotine-like structure and effect.     

Thalidomide pharmacokinetics in sheep

AIM: To determine the half life (T_1/2), time taken to reach maximum plasma concentration (T_max) and maximum plasma concentration (C_max) of thalidomide in sheep following I/V, oral and topical treatment with a single dose of thalidomide.

METHOD: Three groups of 4–6-month-old ram lambs were treated with thalidomide dissolved in dimethylsulphoxide (DMSO). The first group (n=10) was treated I/V with 100?mg thalidomide in 2?mL DMSO; the second group (n=8) received 400?mg thalidomide in 2?mL DMSO orally, and the third group (n=8) had 400?mg thalidomide in 4?mL DMSO applied topically. Plasma samples were collected up to 36 hours after treatment, snap-frozen at ?80°C and analysed for concentrations of thalidomide using high performance liquid chromatography.

RESULTS: Following I/V administration, T_1/2 was 5.0 (SEM 0.4) hours, volume of distribution was 3,372.0 (SEM 244.3) mL/kg and clearance was 487.1 (SEM 46.1) mL/hour.kg. Topical application of 400?mg thalidomide did not increase plasma concentrations. Following oral administration, thalidomide bioavailability was 89%, with T_1/2, T_max, and C_max being 7.2 (SEM 0.8) hours, 3.0 (SEM 0.4) hours and 1,767.3 (SEM 178.1) ng/mL, respectively.

CONCLUSION: Topical administration using DMSO as a solvent did not increase concentrations of thalidomide in plasma. The mean pharmacokinetic parameters determined following oral treatment with 400?mg of thalidomide were similar to those reported in humans receiving a single 400?mg oral dose (T_1/2 7.3 hours; T_max 4.3 hours and C_max 2,820?ng/mL). There is potential for thalidomide to be used as a model for the treatment of chronic inflammatory conditions in sheep, such as Johne's disease, where tumour necrosis factor alpha plays a pathogenic role.