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1.
A clinical dose rate (4.4 mg/kg bodyweight) of phenylbutazone was administered intravenously and orally to six Welsh mountain ponies to provide data on the pharmacokinetics and bioavailability of the drug. In three, three-year-old ponies, clearance of the drug from plasma after intravenous administration was almost twice as rapid as in three ponies aged eight to 10 years. After oral administration, plasma phenylbutazone levels were greater in the older ponies, the area under the plasma concentration time curve being almost twice as high. This did not result from more efficient absorption but from slower plasma clearance. The fractional absorption of phenylbutazone was similar in young and older ponies, 0.78 and 0.75, respectively. The 24 hour urinary excretion of phenylbutazone and its hydroxylated metabolites, oxyphenbutazone and gamma-hydroxyphenylbutazone, accounted for approximately 25 per cent of the administered intravenous dose in both young and older ponies. The possible fate(s) of the remaining 75 per cent were considered.  相似文献   

2.
Aim: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days.

Methods: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded.

Results: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease.

Conclusions: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals.These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep.  相似文献   

3.
AIM: To examine clinical and subclinical effects of sporidesmin administered orally to sheep at very low daily dose rates for periods of 3 to 48 days. METHODS: Two experiments were conducted. In Experiment A, sporidesmin-A was administered orally to groups of 16 sheep at daily dose rates of approximately 0.0042, 0.0083 and 0.0167 mg/kg bodyweight for 48 days. In Experiment B, the highest of these doses was administered orally for 3, 6, 12, 24 or 48 consecutive days. Parameters of production, clinical findings, organ weights and pathological findings were recorded. RESULTS: In Experiment A, severe liver lesions and photosensitisation were evident as early as 18 days after commencement of daily low-dose administration of sporidesmin, and were associated with significant bodyweight loss. Significant bodyweight loss also occurred in non-photosensitised sporidesmin-treated sheep. Bodyweight reductions were associated with reduced carcass weights and skin weights in treated animals. Sporidesmin administration was also associated with reduced bodyweight gains and pathological changes of the liver, kidney, hepatic lymph nodes, thymus, adrenal gland, heart and spleen. In Experiment B, only moderate changes occurred in a few sheep in the groups dosed with sporidesmin at 0.0167 mg/kg for 3 or 6 days, but major changes were frequently recorded in animals dosed at this rate for 12 days or longer. These comprised changes in the liver and other organs, and photosensitisation typical of the disease, facial eczema. Results are discussed in relation to animal welfare and economic issues associated with this disease. CONCLUSIONS: Sporidesmin caused significant clinical and sub-clinical disease and reduced animal production at relatively low daily dose rates. The effects of repeated daily low-dose administration of sporidesmin appear to be cumulative. There was considerable variation in susceptibility between individual animals. These results emphasise the considerable production losses and animal welfare effects associated with sporidesmin toxicity in sheep.  相似文献   

4.
One hundred and twenty-nine dogs with pituitary-dependent hyperadrenocorticism were treated according to a protocol aimed at the complete destruction of the adrenal cortices by the administration of o,p'-DDD (mitotane) at a daily dose of 50 to 75 mg/kg bodyweight for 25 days. On the third day, glucocorticoid and mineralocorticoid supplementation was begun for the induced adrenocortical insufficiency. The first followup examination after completion of the 25-day course and the subsequent twice-yearly follow-up examinations included physical examination and measurements of plasma concentrations of sodium and potassium to optimise substitution therapy. In 19 dogs the full course of 25 days treatment could not be completed. Of the 110 dogs which received the full course of treatment, the administration had to be stopped temporarily in 32 because of side-effects, such as anorexia and vomiting. The actual dose of o,p'-DDD administered was not significantly different in the dogs with and without these side-effects. Clinical remission occurred in 111 dogs (86 per cent), of which 43 (39 per cent) had a relapse. The estimated one-year disease-free fraction was 77 per cent (95 per cent confidence interval [CI]: 67 to 85 per cent). The estimated one-year survival fraction was 80 per cent (95 per cent CI: 71 to 87 per cent), the two-year survival was 69 per cent (95 per cent CI: 59 to 78 per cent), and the three-year survival was 61 per cent (95 per cent CI: 49 to 71 per cent). The bodyweight and age of the dog, and vomiting occurring during the period of treatment, were positively correlated with the length of the disease-free period, whereas weakness during the treatment and resistance to dexamethasone suppression of the urinary corticoid/creatinine ratios at the start of the treatment were associated with a relatively short survival time.  相似文献   

5.
The efficacy of halofuginone lactate in the prevention of cryptosporidiosis in suckling calves was evaluated in a multicentre, control versus placebo, randomised, double-blind clinical trial. Seventy-eight six- to 48-hour-old calves were treated daily with 120 microg/kg bodyweight of halofuginone lactate administered orally for seven consecutive days, while 80 calves received a placebo. Faecal samples were collected on the first day of dosing and four, seven, 14 and 21 days later, and Cryptosporidium parvum oocysts were counted and faecal indices for diarrhoea were determined after a clinical examination. An analysis of variance for repeated measurements showed a highly significant difference in favour of halofuginone lactate for both the oocyst counts (P=0.0002) and the faecal diarrhoea indices (P=0.0001) throughout the trial. The difference was greatest after seven days, when the mean oocyst count of the placebo group was 2.5 times and its mean faecal index was twice the mean of the halofuginone lactate group. One day after the end of the treatment the calves which received halofuginone lactate excreted 44 per cent fewer C parvum oocysts and 44 per cent fewer of them had diarrhoea. The reduction was even greater (65 per cent) when liquid diarrhoea was assessed, with 32.5 per cent of the calves in the placebo group having liquid diarrhoea compared with 11.5 per cent in the halofuginone lactate group. The treatment was well tolerated and easily administered.  相似文献   

6.
A restricted programme of strategic dosing with triclabendazole was used to treat a sheep flock with severe clinical fascioliasis. After five years the percentage of ewes passing fluke eggs was reduced from 49 per cent to less than 1 per cent, without the reappearance of clinical fascioliasis. It is suggested that this programme offers an efficient and practical means of controlling fascioliasis.  相似文献   

7.
Cabergoline, a new prolactin inhibitor, was evaluated clinically in 143 bitches with pseudopregnancy and, or, false lactation, 14 cases of lactation after ovariohysterectomy for the removal of dead fetuses, 12 cases of persisting lactation after early weaning, and five cases of eclampsia. The drug was administered as a once-daily oral treatment (on food) in 139 cases or as subcutaneous injections at 48 hour intervals (maximum four injections) at a dose of 5, 2–5 or 1–5 μg/kg bodyweight in 35 cases. Improvement was evident within three to four days, and in 80 per cent of the cases clinical signs (abnormal behaviour, mammary gland swelling. milk secretion) had been significantly reduced or had disappeared within seven days. Treatment was successful in 95 per cent of the cases. Emesis was the only objectionable clinical side effect, being seen in 3 per cent of orally treated animals and necessitated withdrawal of one dog from the study. Vomiting occurred after the first (65-7 per cent) and second (22-9 per cent) injection only.  相似文献   

8.
Five milligram of megestrol acetate were orally used over ten days during mating periods to synchronise oestrus in caracool sheep. Eighteen days were allowed to elapse from the last administration of progestagen before 1,000 I.U. PMSG were injected to boost fertility. The test reported in this paper had been applied to a large sheep herd over three years. The following conclusions were drawn: Synchronised occurrence of heat in the mating period was not reduced by oral administration of 5 mg megestrol acetate over ten days for a period of three years (87.1 to 95.5 per cent). The fertilisation rate in response to first insemination was between 68.8 and 73.1 per cent. Birth to lambs was given by 85-92 per cent of the ewes after two inseminations. No fertility occurred in 1.5-3.1 per cent of all animals.  相似文献   

9.
Trials were carried out on 11 farms to assess the effectiveness of 2.5 per cent w/v cypermethrin pour-on for the control of ticks on sheep. Treatment at the rate of 5 ml/10 kg bodyweight gave 92 per cent control of ticks on ewes for up to nine weeks and 88 per cent control on lambs for up to eight weeks.  相似文献   

10.
Sheep in a flock in which 88 per cent of the ewes had antibodies to maedi-visna virus were clinically examined for udder induration during lactation and after drying off. On both occasions about half of the ewes had indurated udders. Histological examination revealed lymphocytic mastitis associated with maedi-visna virus infection, in the udders of six of 25 hoggs (24 per cent), 21 of 39 shearlings (53.8 per cent) and 42 of 67 ewes (62.7 per cent). Distinct lung lesions were found in 8 per cent of the hoggs, 12.5 per cent of the shearlings and 10 per cent of the ewes. The results of a clinical examination of dry udders were correlated with the histological findings.  相似文献   

11.
The depolarising muscle relaxant suxamethonium (0.3 mg kg-1) and the non-depolarising relaxant atracurium (0.6 mg kg-1) were administered to four dogs. In the first series of experiments atracurium was administered, followed at 50 per cent return of neuromuscular activity by suxamethonium. At 50 per cent return of activity atropine and neostigmine were administered to reverse the block. In the second series of experiments the sequence was reversed and atracurium was administered after suxamethonium. At 50 per cent recovery atropine and neostigmine were given. In the first series of experiments it was demonstrated that the prior administration of atracurium reduced the duration of action of suxamethonium. However, in the second series it was shown that the prior administration of suxamethonium had no significant effect on the duration of action of atracurium.  相似文献   

12.
Serum, tissue and peritoneal fluid concentrations of ceftazidime were studied in ewes after intravenous, intramuscular and subcutaneous administration at 50 mg kg-1 bodyweight. Tissue and peritoneal cages were implanted in the animals studied. After intravenous bolus administration, the mean serum concentration versus time profile was best described by a two-compartment open model. The distribution rate constant (alpha) was 3.5 +/- 1.1 h-1 and the half-life (t 1/2 alpha) 0.22 +/- 0.09 hour. The elimination rate constant (beta) was 0.43 +/- 0.04 h-1 and half-life (t 1/2 beta) 1.6 +/- 0.2 hours. The area under the curve was 275.7 +/- 84.0 micrograms.ml-1 h. The volume of distribution as steady state was 356.1 +/- 208.0 ml kg-1. The penetration ratio into tissue fluid was 62.6 +/- 15.1 per cent and into peritoneal fluid 61.1 +/- 16.5 per cent. After intramuscular injection, the elimination half-life was 1.7 +/- 0.2 hours, the area under the curve was 228.7 +/- 43.3 micrograms.ml-1 h. and the elimination rate constant was 0.42 +/- 0.05 h-1. The penetration ratio into tissue fluid was 68.5 +/- 37.3 per cent and into peritoneal fluid 73.3 +/- 34.4 per cent. After subcutaneous injection, the elimination half-life was 1.8 +/- 0.5 hours, the area under the curve was 231.8 +/- 65.6 micrograms.ml-1 h. and the elimination constant was 0.41 +/- 0.10 h-1. The penetration ratio into tissue fluid was 47.2 +/- 3.5 per cent and into peritoneal fluid 58.1 +/- 15.6 per cent.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

13.
The administration of melatonin via intravaginal sponges is an effective method of advancing the breeding season in ewes. In the present study the fertility of melatonin-treated ewes has been compared with that of ewes induced to ovulate by conventional treatment. On June 25, 15, 15-month-old ewes (group 1) were given intravaginal implants containing melatonin in silastic tubing. On August 8, 13 similar ewes (group 2) were given Veramix sponges which were removed 12 days later, when they were given 500 iu pregnant mare's serum gonadotrophin (PMSG). Two intact raddled rams were introduced to the combined groups on August 21. The mean date of mating was September 3 +/- 1.5 for group 1 and August 21 +/- 0.2 for group 2 ewes. All the ewes in group 1 and 10 in group 2 (77 per cent) were mated. All the ewes were slaughtered approximately 50 days after mating and their reproductive tracts removed. The mean ovulation rates were 2.1 and 2.3 in groups 1 and 2, respectively. The results indicate that conception rates of 87 per cent and 61.5 per cent of ewes put to the ram were obtained in the melatonin-treated and PMSG-treated groups, respectively. At slaughter the melatonin-treated group were found to have a mean of 1.47 live fetuses per ewe put to the ram and the PMSG-treated group a mean of 1.08. It can therefore be concluded that melatonin implantation is an effective method for the advancement of seasonal breeding in anoestrous sheep, and that the fertility achieved is at least as good as that given by conventional progestogen-PMSG treatment.  相似文献   

14.
Rats undergoing laparotomy received either carprofen (5 mg/kg) or ketoprofen (5 mg/kg) administered orally in flavoured gelatin, or by subcutaneous injection. A control group that received no analgesic showed a significant (3 per cent) fall in bodyweight (P = 0.009) after laparotomy. This decrease was greater than that seen in the groups receiving carprofen (P = 0.006) or ketoprofen (P = 0.012) administered subcutaneously, which continued to gain weight following surgery. All animals showed a significant fall in food consumption but this decrease was greater in the jelly alone group (47 per cent) than in the group receiving carprofen (17 per cent) (P = 0.015) administered subcutaneously. A significant fall in water consumption occurred in the control group (40 per cent) and in animals that received oral carprofen (13 per cent) or Ketoprofen (22 per cent). No significant decrease was seen in groups receiving either carprofen or ketoprofen administered subcutaneously (P > 0.1). This study shows that a relatively simple surgical procedure results in a major reduction in food and water consumption in rats. This reduction can be minimised by the administration of ketoprofen or carprofen (5 mg/kg subcutaneously), but higher dose rates are required if these drugs are to be administered by the oral route.  相似文献   

15.
A paste formulation containing 14.3 per cent of oxibendazole and 44 per cent of trichlorfon was administered to 33 ponies and horses. The dose rate used was equivalent to 10 mg and 30 mg/kg bodyweight, of oxibendazole and trichlorfon respectively. After treatment 25 animals passed between one and 82 third stage larvae of Gasterophilus intestinalis in their faeces. Dosing with 0.2 mg ivermectin/kg bodyweight three weeks later resulted in six animals expelling between one and four bots. The efficacy of the oxibendazole-trichlorfon paste was on average 96.2 per cent. This drug combination given to 52 ponies and horses at the indicated dose rate and to six ponies at twice that dose was tolerated without side effects except transient softening of the faeces in several animals and mild symptoms of colic in two horses.  相似文献   

16.
Forty yearling calves were assigned to four equal groups; three of the groups were treated with oxfendazole at dose rates of 6.75 mg/kg, 4.50 mg/kg, or 2.25 mg/kg bodyweight while the fourth group served as an untreated control. The calves were native to north-east Mississippi, USA, and harboured natural infections of gastrointestinal nematodes. The study was conducted during July when inhibited early fourth-stage larvae may be found in large numbers after their acquisition in the spring. The calves were maintained in separate groups on concrete-floored pens for 17 days before the intraruminal administration of oxfendazole. Seven days after treatment, the calves were slaughtered and the gastrointestinal parasites counted. At all the dose rates examined oxfendazole exhibited an efficacy of at least 99.4 per cent against adults of Haemonchus placei, Trichostrongylus axei, Bunostomum phlebotomum, Cooperia species, T colubriformis, Oesophagostomum radiatum, and Trichuris ovis. The efficacy against adult Ostertagia ostertagi was at least 99.4 per cent at dose rates of 6.75 and 4.50 mg/kg bodyweight, but decreased to 93.7 per cent at 2.25 mg/kg. The efficacy of oxfendazole against inhibited larvae of O ostertagi decreased with dose rate from 78.8 per cent at 6.75 mg/kg, to 58.9 per cent at 4.50 mg/kg and 20.3 per cent at 2.25 mg/kg bodyweight.  相似文献   

17.
A postal census of vaginal prolapse in sheep flocks in the Borders region of Scotland yielded 540 replies from 963 owners (56 per cent). There were 262,250 ewes in 976 flocks and 2573 vaginal prolapses were reported. Analysis of the data revealed that 390 (40 per cent) of the flocks had no vaginal prolapses and in 237 (24.3 per cent) the reported prevalence was between 0.1 per cent and 1.0 per cent. Only 63 (6.5 per cent) of flocks had a greater than 5 per cent prevalence of vaginal prolapses. The greatest number of prolapses occurred in an upland flock of greyface ewes mated with Suffolk tups with 50 cases among 700 ewes (7.1 per cent) and the highest prevalence was in an upland Scottish blackface flock of ewes bred with Suffolk tups with 15.2 per cent (35 cases among 230 ewes). There were marked breed differences; very few hill breeds were affected and most cases occurred in greyface ewes mated with Suffolk tups.  相似文献   

18.
Flunixin pharmacokinetics and serum thromboxane inhibition in the dog   总被引:2,自引:0,他引:2  
Flunixin meglumine administered orally to beagle dogs at doses of 0.55, 1.10 or 1.65 mg/kg bodyweight was rapidly absorbed to produce maximum mean plasma concentrations of 2.40 +/- 0.70, 4.57 +/- 1.12 and 7.42 +/- 2.07 micrograms/ml, respectively. Thereafter, the plasma concentrations of flunixin fell rapidly to values less than 0.10 micrograms/ml from 24 hours after drug administration at all dosage levels. The maximum mean inhibition of serum thromboxane B2 was 91.5 per cent after the lowest dose of flunixin and 98.8 per cent for both the intermediate and high dose rates. At plasma concentrations of flunixin above 2 micrograms/ml there was more than 90 per cent inhibition of thromboxane.  相似文献   

19.
The aim of the present study was to investigate the effects of intravenously administered sulfadoxine (5 mg kg −1 bodyweight) or sulfaphenazole (5 mg kg−1 bodyweight) on the in vivo elimination of i.v. tolbutamide (5 mg kg−1 bodyweight), as both compounds were shown to inhibit tolbutamide hydroxylation in vitro. It was shown that relative large differences in tolbutamide clearance exist among goats (n = 6). A high correlation was seen between tolbutamide and sulfadoxine clearances. Tolbutamide clearance was significantly reduced by concommitant administration of sulfaphenazole. Sulfadoxine ( ) had a less consistent effect. Mean tolbutamide plasma clearance was not significantly affected due to the fact that three animals showed an inhibition, whereas three others apparently did not respond. A negative correlation was found between the amount of N4-acetyl in urine and the clearance. Approximately 93 per cent of tolbutamide was bound to plasma proteins. However, there was no evidence for displacement of tolbutamide from its protein binding sites by sulfaphenazole or sulfadoxine. The results described in the present study confirm previous in vitro data obtained with goat hepatocytes. Although quantitative differences in inhibition exist between in vivo and in vitro results, hepatocytes are a good model to study potential drug-drug interactions at the level of biotransformation processes.  相似文献   

20.
This prospective study aimed to record the toxicity profile of a dose-intensifying simultaneous chemotherapy (DISC) protocol for lymphoma in dogs. Remission rates and the duration of the protocol were also evaluated. Twenty-one dogs were studied. Diagnosis was based on cytological or histological assessments. The DISC protocol is a 13-week maintenance-free protocol. L-Asparaginase (400 iu/kg) was administered subcutaneously on day 1, followed by weekly simultaneous intravenous administration of vincristine (0.7 mg/m(2) = 100 per cent), cyclophosphamide (200 mg/m(2) = 100 per cent) and doxorubicin (30 mg/m(2) = 100 per cent) at a starting dose level of 33 per cent. Dose levels were given twice and then increased by 5 to 7 per cent if grade 0 or I toxicities were seen, to a maximum dose level of 60 per cent. Two dogs experienced a grade IV toxicity (asymptomatic neutropenia in one dog and sepsis in the other). Two episodes of asymptomatic grade III thrombocytopenia and one episode of neutropenia were recorded. Other toxic events were infrequent and mild. Only one dog required hospitalisation for less than 72 hours. Seventeen dogs (80.9 per cent) achieved complete remission, one (4.8 per cent) achieved partial remission, two (9.5 per cent) had stable disease and in one (4.8 per cent) disease progressed.  相似文献   

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