Clostridium perfringens epsilon toxin inhibits the gastrointestinal transit in mice

Epsilon toxin produced by Clostridium perfringens type B and D is a potent toxin that is responsible for a highly fatal enterotoxemia in sheep and goats. In vitro, epsilon toxin produces contraction of the rat ileum as the result of an indirect action, presumably mediated through the autonomic nervous system. To examine the impact of epsilon toxin in the intestinal transit, gastric emptying (GE) and gastrointestinal transit (GIT) were evaluated after intravenous and oral administration of epsilon toxin in mice. Orally administered epsilon toxin produced a delay on the GIT. Inhibition of the small intestinal transit was observed as early as 1 h after the toxin was administered orally but the effects were not observed after 1 week. Epsilon toxin also produced an inhibition in GE and a delay on the GIT when relatively high toxin concentrations were given intravenously. These results indicate that epsilon toxin administered orally or intravenously to mice transitorily inhibits the GIT. The delay in the GIT induced by epsilon toxin could be relevant in the pathogenesis of C. perfringens type B and D enterotoxemia.     

Hepatoencephalopathy syndrome due to Cassia occidentalis (Leguminosae,Caesalpinioideae) seed ingestion in horses

Cassia occidentalis is a bush from the Leguminosae family, subfamily Caesalpinoideae, and is a toxic plant of veterinary interest due to the occasional contamination of animal rations. This report describes the clinical and histopathological findings of an outbreak of C. occidentalis poisoning in horses. Twenty mares were poisoned after consuming ground corn contaminated with 8% of C. occidentalis seeds. Of the 20 animals affected, 12 died: 8 mares were found dead, 2 died 6 h after the onset of clinical signs compatible with hepatic encephalopathy and the 2 other animals were subjected to euthanasia 12 h after the onset of the clinical signs. The remaining 8 mares presented with mild depression and decreased appetite, but improved with treatment and no clinical sequelae were observed. In 6 animals that underwent a necropsy, an enhanced hepatic lobular pattern was noted and within the large intestine, a large number of seeds were consistently observed. Hepatocellular pericentrolobular necrosis and cerebral oedema were the main histological findings. In one mare, there was mild multifocal semimembranosus rhabdomyocytic necrosis and haemorrhage. Seeds collected from intestinal contents and sifted from the culpable feedstuff were planted. Examination of the leaves, flowers, fruits and seeds of the resultant plants identified C. occidentalis. Horses poisoned by C. occidentalis seeds demonstrate clinical signs associated with hepatoencephalopathy and frequently die suddenly. Lesions primarily involve the liver and secondarily, the central nervous system. Cassia occidentalis poisoning should be considered a differential diagnosis in horses with hepatoencephalopathy and special caution should be taken with horse rations to avoid contamination with seeds of this toxic plant.     

Physiological responses of transported goats treated with ascorbic acid during the hot-dry season

The aim of the present study was to determine the physiological responses of transported Red Sokoto goats (RSG) treated with ascorbic acid (AA). Ten RSG treated orally with ascorbic acid served as experimental subjects, while seven goats treated with sterile water served as the control. The goats were transported for 8 h. The ambient temperature and relative humidity during the study period fluctuated between 21 and 38°C and 51 and 91%, respectively, which indicated that the season was thermally stressful and did not favor transportation of goats. The rectal temperature obtained in the control goats was significantly higher (P < 0.01) than the value in the experimental goats after transportation. There was a significant decrease (P < 0.05) in eosinophil counts and an increase (P < 0.01) in neutrophil counts and neutrophil : lymphocyte ratio recorded in the control goats after transportation, which suggested that the control goats were physically and emotionally stressed. The control goats lost 11.9% of their initial liveweight, while the experimental goats lost only 1.04% after transportation. Multiple stresses, including extreme meteorological factors, acted upon the transported goats and impaired their homeostatic mechanism. In conclusion, AA administration in goats reduced the adverse effects of road transportation stress.     

Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition

Ballent, M., Lifschitz, A., Virkel, G., Mate, L., & Lanusse, C. Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition. J. vet. Pharmacol. Therap. 33 , 252–259. The goal of the study was to evaluate the effects of rifampicin (RFP) and phenobarbital (PBT) on the plasma and gastrointestinal disposition kinetics of ivermectin (IVM) subcutaneously administered to Wistar rats. Fifty seven rats were used. Animals in Group I were the noninduced (control) group. Those in Groups II and III received a treatment with RFP (160 mg/day) and PBT (35 mg/day), respectively, both given orally during eight consecutive days as induction regimen. The IVM pharmacokinetic study was started 24 h after the RFP and PBT last administration. Animals received IVM (200 μg/kg) by subcutaneous injection. Rats were sacrificed between 6 h and 3 days after IVM administration. Blood and samples of liver tissue, intestinal wall and luminal content of jejunum were collected from each animal. IVM concentrations were measured by high performance liquid chromatography. IVM disposition kinetics in plasma and tissues was significantly modified by the PBT treatment, but not by RFP. Despite the enhanced CYP3A activity observed after the pretreatment with RPF and PBT, there were no marked changes on the percentages of IVM metabolites recovered from the bloodstream in induced and noninduced animals. An enhanced P‐glycoprotein‐mediated intestinal transport activity in pretreated animals (particularly in PBT pretreated rats) may explain the drastic changes observed on IVM disposition.     

Proliferation and transmission patterns of <Emphasis Type="Italic">Pasteurella multocida</Emphasis> B:2 in goats

This report describes the proliferation and transmission patterns of Pasteurella multocida B:2 among stressful goats, created through dexamethasone injections. Thirty seven clinically healthy adult goats were divided into three groups consisted of 15 goats in group A, 11 goats in group B and the remaining 11 in group C. At the start of the study, all goats of group A were exposed intranasally to 1.97 × 10¹⁰ CFU/ml of live P. multocida B:2. Dexamethasone was immediately administered intramuscularly for 3 consecutive days at a dosage rate of 1 mg/kg. The exposed goats were observed for signs of HS for a period of 1 month. At the end of the 1-month period, 11 goats from group B were introduced into and commingled with the surviving goats of group A before all goats from both groups were immediately injected intramuscularly with dexamethasone for 3 consecutive days. The treatment with dexamethasone was then carried out at monthly interval throughout the 3-month study period. Goats of group C were kept separately as negative control. Three surviving goats from each group were killed at 2-week interval for a complete post-mortem examination. Two (13%) goats of group A were killed within 24 hours after intranasal exposure to P. multocida B:2 while another two (13%) goats from the same group were killed on day 40, approximately 10 days after the second dexamethasone injection. All four goats showed signs and lesions typical of haemorrhagic septicaemia. Bacteraemia was detected in 3 goats of group A that were having rectal temperature higher than 41°C. The P. multocida B:2 isolation pattern was closely associated with dexamethasone injections when significantly (p < 0.05) higher rate of isolations from both groups were observed after each dexamethasone injection. Transmission of P. multocida B:2 from goats of group A to group B was successful when P. multocida B:2 was isolated from goats of group B for a period of 28 days. There was a strong correlation between dexamethasone injections, rate of bacterial isolation and serum cortisol level. The IgG level showed an increasing trend 2 weeks after exposure to P. multocida B:2 and remained high throughout the study period.     

Preliminary Observations on Experimental Ruta graveolens Toxicosis in Nubian Goats

We present the first reported study of Ruta graveolens toxicity in 7–8-month-old Nubian goats. Oral administration of 5 g/kg bw per day of R. graveolens leaves caused tremor, dyspnoea, frequent urination, incoordination of movement, ataxia and recumbency, with death after 1–7 days. In goats receiving oral doses of 1 g/kg bw per day of the leaves, the course of toxicity was prolonged and the animals had pallor of the visible mucous membranes and loss in condition; one died on day 17, the others being slaughtered on days 41 and 46. The clinical effects were correlated with pathological changes in various organs, alterations in serum aspartate transaminase, creatine kinase, total protein, cholesterol, urea and other serum constituents, haematological values and the concentrations in the tissues of copper, iron, zinc, manganese, calcium and phosphorus.     

Pharmacokinetics of meloxicam in adult goats: a comparative study of subcutaneous,oral and intravenous administration

AIMS: To determine the plasma disposition of meloxicam in goats following S/C, oral or I/V administration at a single dose of 0.5?mg/kg bodyweight.

METHODS: Five healthy Saanen goats, aged 12–14 months and weighing 35–40?kg, were used for a three phase cross-over design with a 10-day washout period, with meloxicam administered I/V, then orally and S/C. Heparinised blood samples (5?mL) were collected from all animals prior to drug administration (0 hours) and subsequently up to 96 hours. Concentrations of meloxicam in plasma were measured using high performance liquid chromatography. Concentration-time curves were fitted and pharmacokinetic parameters were estimated for each administration group.

RESULTS: Subcutaneous administration of meloxicam exhibited unique plasma distribution characteristics that differed from oral and I/V administration. Mean peak plasma concentrations were greater (1.91 (SD 0.39) vs. 0.71 (SD 0.17) µg/mL) and the time to reach them shorter (3.20 (SD 1.64) vs. 14.33 (SD 2.19) hours) following S/C compared with oral administration (p<0.05). The terminal half-life was longer (15.16 (SD 4.74) vs. 10.69 (SD 1.49) hours) and the MRT was shorter (15.67 (SD 2.37) vs. 24.33 (SD 3.12) hours) following S/C than oral administration (p<0.05), but bioavailability was similar (98.24 (SD 9.62) vs. 96.49 (SD 10.71)%).

CONCLUSION AND CLINICAL RELEVANCE: Subcutaneous administration of meloxicam resulted in long-term presence of drug at high concentration in goat plasma. This unique plasma disposition characteristic may offer an advantage in some clinical cases towards potentially improving the treatment efficacy in goats.     

Effects of endotoxin-induced fever and probenecid on disposition of enrofloxacin and its metabolite ciprofloxacin after intravascular administration of enrofloxacin in goats

Pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in normal, febrile and probenecid‐treated adult goats after single intravenous (i.v.) administration of enrofloxacin (5 mg/kg). Pharmacokinetic evaluation of the plasma concentration–time data of enrofloxacin and ciprofloxacin was performed using two‐ and one‐compartment open models, respectively. Plasma enrofloxacin concentrations were significantly higher in febrile (0.75–7 h) and probenecid‐treated (5–7 h) goats than in normal goats. The sum of enrofloxacin and ciprofloxacin concentrations in plasma ≥0.1 μg/mL was maintained up to 7 and 8 h in normal and febrile or probenecid‐treated goats, respectively. The t1/2β, AUC, MRT and ClB of enrofloxacin in normal animals were determined to be 1.14 h, 6.71 μg.h/mL, 1.5 h and 807 mL/h/kg, respectively. The fraction of enrofloxacin metabolized to ciprofloxacin was 28.8%. The Cmax., t1/2β, AUC and MRT of ciprofloxacin in normal goats were 0.45 μg/mL, 1.79 h, 1.84 μg.h/mL and 3.34 h, respectively. As compared with normal goats, the values of t1/2β (1.83 h), AUC (11.68 μg ? h/mL) and MRT (2.13 h) of enrofloxacin were significantly higher, whereas its ClB (430 mL/h/kg) and metabolite conversion to ciprofloxacin (8.5%) were lower in febrile goats. The Cmax. (0.18 μg/mL) and AUC (0.99 μg.h/mL) of ciprofloxacin were significantly decreased, whereas its t1/2β (2.75 h) and MRT (4.58 h) were prolonged in febrile than in normal goats. Concomitant administration of probenecid (40 mg/kg, i.v.) with enrofloxacin did not significantly alter any of the pharmacokinetic variables of either enrofloxacin or ciprofloxacin in goats.     

Pharmacokinetics of ceftiofur crystalline free acid after single subcutaneous administration in lactating and nonlactating domestic goats (Capra aegagrus hircus)

Doré, E., Angelos, J. A., Rowe, J. D., Carlson, J. L., Wetzlich, S. E., Kieu, H. T., Tell, L. A. Pharmacokinetics of ceftiofur crystalline free acid after single subcutaneous administration in lactating and nonlactating domestic goats (Capra aegagrus hircus). J. vet. Pharmacol. Therap. 34 , 25–30. Six nonlactating and six lactating adult female goats received a single subcutaneous injection of ceftiofur crystalline free acid (CCFA) at a dosage of 6.6 mg/kg. Blood samples were collected from the jugular vein before and at multiple time points after CCFA administration. Milk samples were collected twice daily. Concentrations of ceftiofur and desfuroylceftiofur‐related metabolites were measured using high‐performance liquid chromatography. Data were analyzed using compartmental and noncompartmental approaches. The pharmacokinetics of CCFA in the domestic goat was best described by a one compartment model. Mean (±SD) pharmacokinetic parameters were as follows for the nonlactating goats: area under the concentration time curve_0–∞ (159 h·μg/mL ± 19), maximum observed serum concentration (2.3 μg/mL ± 1.1), time of maximal observed serum concentration (26.7 h ± 16.5) and terminal elimination half life (36.9 h; harmonic). For the lactating goats, the pharmacokinetic parameters were as follows: area under the concentration time curve_0–∞ (156 h·μg/mL ± 14), maximum observed serum concentration (1.5 μg/mL ± 0.4), time of maximal observed serum concentration (46 h ± 15.9) and terminal elimination half life (37.3 h; harmonic). Ceftiofur and desfuroylceftiofur‐related metabolites were only detectable in one milk sample at 36 h following treatment. There were no significant differences in the pharmacokinetic parameter between the nonlactating and lactating goats.     

The clinical,biochemical, haematological and pathological effects of long-term administration of Ipomoea carnea to growing goats

Ipomoea carnea has been held responsible for several poisoning episodes, mainly in goats. This plant contains swainsonine, which inhibits acid or lysosomal -mannosidase enzyme, causing cellular vacuolization. The objective of this study was to evaluate I. carnea toxicosis when four different doses of this plant were fed to growing goats. Twenty-five male goats were divided into five groups, one control group and four experimental groups that received 2.5, 5.0, 10.0 and 30.0 g of the plant per kg of live weight per day for 4 months. Blood samples were collected for haematological and biochemical determinations and fragments from some tissues were collected for histopathological study. All the experimental goats ingested the plant throughout the trial, presenting nystagmus, muscle tremors, weakness of the hind limbs and ataxia. They also had a significant increase in alanine aminotransferase (ALT) from the sixth week of the experiment compared to the goats in the control group. There was a significant reduction in haemoglobin concentration in the goats treated with I. carnea. Histopathology revealed degenerative vacuolar alterations in the liver, pancreas, thyroid and kidney cells, and in the neurons of the central nervous system in the animals that received the plant. All these alterations occurred in a dose-dependent manner.     

14C]-aflatoxin B1 metabolism in lactating goats and rats

Four dairy goats in the second to third month of lactation were administered [14C]-Aflatoxin B1 ( [14C]-AFB1). Two goats were dosed intravenously (iv) with 130 muCi (182 muCi/mumol) and two were dosed orally with 196 muCi (256 muCi/mumol). Urine, milk and feces were collected for 120 h after [14C]-AFB1 administration. Recoveries (average of two animals) of 14C in urine, milk and feces were, respectively; 22.7, .97 and 65% (iv dose) and 30.9, 1.05 and 52.3% (oral dose). Aflatoxin M1 (AFM1) was found in milk in the highest concentration. Aflatoxin Q1 (AFQ1) and aflatoxicol (AFL) were found in trace quantities in milk of animals administered the oral dose. In general, AFM1 could account for the majority of dicholromethane-soluble 14C. Liver contained 7.3 and 4.9% of the dose after 120 h for the iv and oral doses respectively. Kidney, heart, lung and spleen all contained .1% or less of the dose at 120 h. Muscle contained .48% of the dose at 120 h from the goats administered [14C]-AFB1 orally. There was no detectable radioactivity in the fat of any goat at 120 h. Six lactating Sprague-Dawley rats with 12 nursing pups were used for comparison of ruminants and simple-stomached animals. Rats were administered 2 muCi of [14C]-AFB1 (125 muCi/mumol) iv (three animals) and orally (three animals). Mean recovery of 14C in urine, mammary plus milk and feces were, respectively; 9.5, 2.0 and 60.7% (iv) and 8.8, 2.6 and 65.0% (orally).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of fasting on the plasma disposition of triclabendazole following oral administration in goats

This study was designed to investigate the effect of feeding on the plasma disposition of triclabendazole (TCBZ) in goats following oral administration. A total of eight goats, aged 14–16 months and weighing 20–30 kg were used in this study. The animals were allocated into two groups (fasted and fed groups) of four animals each. The goats in fed group were fed ad libitum but the animals in fasted group were not fed 24 h before and 6 h after drug administration. Commercial oral drench formulation of TCBZ (Endex-K, 5%) was administered orally to animals in two groups at dose of 10 mg/kg bodyweight. Heparinized blood samples were collected between 1 and 192 h after treatment and the plasma samples were analysed by high performance liquid chromatography (HPLC) for TCBZ, TCBZ sulphoxide (TCBZ–SO), and TCBZ sulphone (TCBZ–SO₂). Relatively very low concentration of TCBZ parent drug was detected between 2 and 48 h, but TCBZ–SO and TCBZ–SO₂ metabolites were present between 2 and 192 h in the plasma samples of fed and fasted animals. Fasting significantly enhanced the plasma concentration of TCBZ and its metabolites. The availability of TCBZ, TCBZ–SO and TCBZ–SO₂ in the plasma samples of fasted goats were markedly greater compared to those of fed goats. It was concluded that fasting decreases the digesta flow rate and prolongs the retention of the drug into the gastrointestinal tract, resulting in enhanced quantitative gastrointestinal absorption or systemic availability of TCBZ and its metabolites in fasted goats.     

Pulmonary function changes in goats given 3-methylindole orally

Six adult goats were given 0.2 g of 3-methylindole (3MI)/kg of body weight orally. Lung mechanics and ventilatory function were obtained before 3MI and 2, 4, 6, 24, 48, and 72 hours after 3MI administration. Clinical signs were also monitored. Lungs were removed for gross and microscopic examination and for morphometric analysis from goats that died spontaneously or were killed with an overdose of pentobarbital after 72 hours. The major pulmonary function changes observed included a marked decrease in dynamic lung compliance with a moderate increase in airway resistance, a concomitant hypoxemia, sustained increase in respiratory frequency, a progressive decrease in tidal volume and alveolar ventilation, and increased dead space to tidal volume ratio. A mild metabolic acidosis was also noticed.     

Preliminary findings from an experimental study of caprine besnoitiosis in Kenya

Inoculation of cystozoites obtained from natural, chronic cases of caprine besnoitiosis produced clinical disease in goats but not in rabbits, mice, guinea pigs, hamsters, rats or cattle. Histological examination of tissue sections from the experimental animals showedBesnoitia cysts only in goats. This, together with field observations that cattle reared together with goats having besnoitiosis do not contract the disease, suggests that theBesnoitia species that infects goats in Kenya is host-specific and is notBesnoitia besnoiti. We suggest that the nameBesnoitia caprae be adopted for the caprine pathogen.     

Pharmacokinetics of single‐dose oral ponazuril in weanling goats

Ponazuril (toltrazuril sulfone) is a triazine antiprotozoal agent that targets apicomplexan organisms. Ponazuril may have clinical application in the treatment of clinical coccidiosis due to Eimeria species in goats, along with other protozoal infections. To evaluate the absorption, distribution and elimination characteristics of ponazuril in goats, a sensitive, validated high‐pressure liquid chromatography and mass spectroscopy method for ponazuril in caprine plasma was developed. After a single oral dose of ponazuril at 10 mg/kg, plasma samples from seven weanling goats were collected and assayed. Plasma concentrations of ponazuril in the goats peaked at 36 ± 13 h post drug administration at a concentration of 9 ± 2 μg/mL. Concentrations declined to an average of 4.2 ± 0.8 μg/mL after 168 h with an average elimination half‐life of 129 ± 72 h post drug administration. This study shows that ponazuril is relatively well absorbed after a single oral dose in goats. Efficacy trials are underway to determine clinical efficacy of ponazuril in the treatment of clinical coccidiosis in goats at 10 mg/kg dosage.     

Toxicity of chlorpyrifos in Nubian goats.

A single oral administration of chlorpyrifos to Nubian goats at 1200, 600 and 300 mg/kg caused nervous signs and death within 15 minutes to 2 days of treatment. An oral dose of the compound at 150 mg/kg was toxic, but not fatal to goats. Animals given chlorpyrifos orally at daily doses of 300, 150 and 75 mg/kg showed signs of toxicity and died within 2 to 7 days of treatment. Pathological, biochemical and haematological changes are described.     

The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour-on administration in goats

Gokbulut, C., Cirak, V.Y., Senlik, B., Aksit, D., McKellar, Q.A. The effects of different ages and dosages on the plasma disposition and hair concentration profile of ivermectin following pour‐on administration in goats. J. vet. Pharmacol. Therap. 34 , 70–75. The effects of different ages and dosages on the plasma disposition and hair degradation of ivermectin (IVM) were investigated following pour‐on administration in goats. Twenty‐eight female Saanen goats allocated into two groups of 14 animals according to their ages as young (5–6 months old) and old (12–24 months old) groups. Each age group was divided into two further of seven goats and administered pour‐on formulation of IVM topically at the in recommended dosage rate of 0.5 mg/kg bodyweight The recommended cattle dosages rate of 0.5 mg/kg or at the higher dosage of 1.0 mg/kg. Blood samples were collected at various times between 1 h and 40 days. In addition, hair samples (>0.01 g) were collected using tweezers from the application sites and far from application sites of the all animals throughout the blood sampling period. The plasma and hair samples were analyzed by high performance liquid chromatography (HPLC) using fluorescence detection following solid and liquid phase extractions, respectively. Dose‐ and age‐dependent plasma disposition of IVM were observed in goats after pour‐on administration. In addition, relatively high concentration and slow degradation of IVM in hair samples collected from the application site and far from the application site were observed in the present study. The differences between young and old goats are probably related to differences in body condition and/or lengths of haircoat. The systemic availability of IVM following pour‐on administration is relatively much lower than after oral and subcutaneous administrations but the plasma persistence was prolonged. Although, the longer persistence of IVM on hairs on the application site may prolong of efficacy against ectoparasites, the poor plasma availability could result in subtherapeutic plasma concentrations, which may confer the risk of resistance development in for internal parasites after pour‐on administration in goats.     

Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals

Chaffin, M. K., Fajt, V., Martens, R. J., Arnold, C. E., Cohen, N. D., O’Conor, M., Taylor, R. J., Bernstein, L. R. Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01150.x. Gallium is a trivalent semi‐metal with anti‐microbial effects because of its incorporation into crucial iron‐dependent reproductive enzyme systems. Gallium maltolate (GaM) provides significant gallium bioavailability to people and mice following oral administration and to neonatal foals following intragastric administration. To study the prophylactic and therapeutic effects of GaM against Rhodococcus equi pneumonia in foals, we developed a methylcellulose formulation of GaM (GaM‐MCF) for oral administration to neonatal foals. Normal neonatal foals were studied. Six foals received 20 mg/kg and another six foals received 40 mg/kg of GaM‐MCF orally. Serial serum samples were collected and serum gallium concentrations were determined using inductively coupled plasma mass spectroscopy. Gallium was rapidly absorbed (T_max of 4 h), and a mean C_max of 0.90 or 1.8 μg/mL was achieved in foals receiving 20 or 40 mg/kg respectively. Marked variability existed in C_max among foals: only half of the foals receiving 20 mg/kg attained serum concentrations of >0.7 μg/mL, a level suggested to be therapeutic against R. equi by previous studies. Mean elimination half‐life was 32.8 or 32.4 h for foals receiving 20 or 40 mg/kg respectively. The results of this study suggest that at least 30 mg/kg orally every 24 h should be considered in future pharmacodynamic and efficacy studies.     

Effects of hypothalamic dopamine on growth hormone‐releasing hormone‐induced growth hormone secretion and thyrotropin‐releasing hormone‐induced prolactin secretion in goats

The aim of the present study was to clarify the effects of hypothalamic dopamine (DA) on the secretion of growth hormone (GH) in goats. The GH‐releasing response to an intravenous (i.v.) injection of GH‐releasing hormone (GHRH, 0.25 μg/kg body weight (BW)) was examined after treatments to augment central DA using carbidopa (carbi, 1 mg/kg BW) and L‐dopa (1 mg/kg BW) in male and female goats under a 16‐h photoperiod (16 h light, 8 h dark) condition. GHRH significantly and rapidly stimulated the release of GH after its i.v. administration to goats (P < 0.05). The carbi and L‐dopa treatments completely suppressed GH‐releasing responses to GHRH in both male and female goats (P < 0.05). The prolactin (PRL)‐releasing response to an i.v. injection of thyrotropin‐releasing hormone (TRH, 1 μg/kg BW) was additionally examined in male goats in this study to confirm modifications to central DA concentrations. The treatments with carbi and L‐dopa significantly reduced TRH‐induced PRL release in goats (P < 0.05). These results demonstrated that hypothalamic DA was involved in the regulatory mechanisms of GH, as well as PRL secretion in goats.     

Pharmacokinetics of Pefloxacin in Goats after Intravenous or Oral Administration

The plasma concentrations and pharmacokinetics of the fluoroquinolone antimicrobial agent pefloxacin, following the administration of a single intravenous (10 mg/kg) or oral (20 mg/kg) dose, were investigated in healthy female goats. The antimicrobial activity in plasma was measured at predetermined times after drug administration by an agar well diffusion microbiological assay, using Escherichia coli (ATCC 25922) as the test organism. Concentrations of the drug 0.25 g/ml were maintained in plasma for up to 6 and 10 h after intravenous (IV) or oral administration of pefloxacin, respectively. The concentration–time data for pefloxacin in plasma after IV or oral administration conformed to two- and one-compartment open models, respectively. Plasma pefloxacin concentrations decreased rapidly during the initial phase after IV injection, with a distribution half-life (t _1/2 ) of 0.10±0.01 h. The terminal phase had a half-life (t _1/2 ) of 1.12±0.21 h. The volume of distribution at steady state (V _dss), mean residence time (MRT) and total systemic clearance (Cl_B) of pefloxacin were 1.08±0.09 L/kg, 1.39±0.23 h and 821±88 (ml/h)/kg, respectively. Following oral administration of pefloxacin, the maximum concentration in the plasma (C _max) was 2.22±0.48 g/ml and the interval from administration until maximum concentration (t _max) was 2.3±0.7 h. The absorption half-life (t _{1/2 ka}), mean absorption time (MAT) and elimination half-life of pefloxacin were 0.82±0.40, 4.2±1.0 and 2.91±0.50 h, respectively. The oral bioavailability of pefloxacin was 42%±5.8%. On the basis of the pharmacokinetic data, a dosage regimen of 20 mg/kg, IV at 8 h intervals or orally twice daily, is suggested for treating infections caused by drug-sensitive pathogens in goats.