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1.
The effect of phenylbutazone on gastric emptying in horses was determined by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal fasted horses (n = 6), horses given endotoxin intravenously (n = 6), horses given intravenous phenylbutazone (n = 6), and horses given intravenous phenylbutazone plus endotoxin (n = 6). The mean time to reach maximum serum acetaminophen concentration (Tmax), the maximum serum concentration (Cmax), and the area under the serum acetaminophen concentration versus time curve (AUC) were compared among treatment groups. Phenylbutazone did not alter gastric emptying in normal horses. Endotoxin caused a profound delay in gastric emptying, and pretreatment with phenylbutazone abolished this effect.  相似文献   

2.
This study was designed to evaluate possible organ and system disorders associated with experimentally induced levamisole poisoning in dogs. For this purpose, twelve clinically healthy dogs of different ages, sexes and breeds were used. They were divided into two equal groups (Group A and Group B) and given levamisole orally at a dose of 25 mg/kg of body weight daily for three days. The dogs in Group B were also injected with atropin sulphate (0.04 mg/kg of body weight) subcutaneously (sc) 1 hour after each administration of levamisole. Routine clinical examinations were made and some haematological, biochemical and blood gas parameters were established at various times after administration of levamisole. The dogs in Group A developed severe neurological signs, gastric haemorrhage, bloody vomiting, colic, anaemia and four dogs died. In Group B these signs were mild and only one dog died. Levamisole poisoning was characterised by a significant reduction in the total number of red blood cells (RBCs), concentration of haemoglobin (Hb) and packed cell volume (PCV), and by anaemia. Peripheral blood pH, actual bicarbonate of plasma (HCO3), actual base excess (BE), partial pressure of oxygen (pO2) and saturated oxygen (O2SAT) increased in both groups of animals and these dogs developed metabolic alkalosis 48 hours after the first administration of levamisole. The results of the study also show that levamisole poisoning in dogs causes a significant increase in the activity of serum alanine aminotransferase (ALT) and of alkaline phosphatase (AP) and in the concentration of urea in both Group A and Group B. In the study, atropin sulphate reduced the severity of the clinical signs and the number of deaths, but it was not alone sufficient to remedy levamisole poisoning in dogs.  相似文献   

3.
Biochemical and haematological effects of phenylbutazone in horses   总被引：1，自引：0，他引：1  
Five matched pairs of horses were used to investigate the effects of phenylbutazone on a range of physiological, biochemical and haematological variables. The drug was given by mouth daily for 15 consecutive days at the manufacturer's recommended dose rates to one group of horses (Group A); the second group (Group B) received equivalent doses of a placebo. For some of the measured parameters, significant changes were recorded in both groups, indicating background instability. Significant decreases in serum total protein, albumin, plasma pH, viscosity and magnesium, and an increase in albumin: globulin ratio occurred in Group A, but not in Group B. These changes were, therefore, attributed to phenylbutazone or its metabolites. Toxicologically, the change in pH is probably unimportant but the decrease in protein concentration may have resulted from a protein losing enteropathy and/or from decreased synthesis in the liver. In one animal which received phenylbutazone, clinical signs of toxicity (lethargy, inappetence, oedema) were observed and evidence of hepatotoxicity and haematological changes were also noted in this horse. It is concluded that recommended dose rates of phenylbutazone should never be exceeded and that the period for which the highest dose (4.4 mg/kg body weight twice daily for four days) is administered should be reduced. In clinical cases, where phenylbutazone toxicity is suspected, measurement of serum or plasma protein concentration might provide an indication of the need to reduce dose levels or stop therapy.  相似文献   

4.
Serum and urinary phenylbutazone (PBZ) concentrations were measured for eight Thoroughbred mares following four daily oral doses and one IV dose of PBZ per mare. Urine flow was estimated from urinary creatinine concentration. The serum PBZ concentration significantly correlated with the urinary concentration, but only about half of the variation in serum PBZ concentrations was explained by the linear relationship with urinary PBZ concentration (R2=0.48). Correlation of serum PBZ concentration with urinary PBZ excretion, which was estimated using urinary creatinine concentration, over half of the variation in serum PBZ concentrations: (R2=0.60).  相似文献   

5.
Simultaneous administration of a nonselective COX inhibitor and a COX‐2 specific NSAID has not been previously reported in horses. The goal of this study was to determine the safety of a 10‐day dosage regimen of phenylbutazone and firocoxib, both at their standard dosages, in horses. Six horses were administered 2.2 mg/kg of phenylbutazone and 0.1 mg/kg of firocoxib by mouth, daily for 10 days. Horses were assessed daily for changes in behavior, appetite, fecal consistency, signs of abdominal pain, and oral mucous membrane ulceration. Horses were assessed prior to and on the last day of treatment for changes in serum creatinine, albumin, total protein, and urine‐specific gravity. Horses underwent endoscopic examination of the esophagus, stomach, and pylorus prior to and 24 hours after the last treatment. A significant change in serum creatinine and total protein was observed on day 10 of treatment. No other significant findings were noted during the experiment. Results indicated that co‐administration of phenylbutazone and firocoxib may cause renal disease.  相似文献   

6.
To determine the rate of urine flow and thus urinary excretion in the horse from untimed urine samples alone, the flow rate, creatinine concentration, osmolarity, and refractive index of 228 quantitatively collected urine samples were determined in 53 experiments on 12 healthy Thoroughbred mares. Forty samples were collected after water-induced diuresis; 11 samples were collected after furosemide-induced diuresis. Flow rates, which ranged from 1.2 to 84.5 ml/min, could be predicted from the urinary creatinine concentration. Correlation of urinary flow with urinary creatinine concentration accounted for 94% of the variability in the urinary flow rates. Phenylbutazone was administered before collection of 168 urine samples. Urine flow rates that were predicted from urinary creatinine concentration were used to estimate phenylbutazone excretion. Urine flow could be estimated without quantitative urine collection.  相似文献   

7.
The objectives of this study were to determine if phenylbutazone decreased serum thyroxine (TT4) and free thyroxine (FT4) concentrations using radioimmunoassay and equilibrium dialysis techniques in horses, and, if so, an additional objective was to determine the duration of this decreased concentration once phenylbutazone administration was discontinued. Serum TT4 and FT4 concentrations were determined before and after administration of 4.4 mg/kg of phenylbutazone IV bid for 5 days. Treatment with phenylbutazone caused a significant decrease in TT4 and FT4 concentrations ( P < .05). Serum TT4 concentration significantly decreased after day 4 of treatment and remained significantly below baseline value for 10 days after discontinuing phenylbutazone administration; it returned to a value not different from the baseline value by the 11th day. Serum FT4 concentration significantly decreased after day 4 of treatment and remained significantly below the baseline value for only 1 day after phenylbutazone administration was discontinued; it returned to a value not different from the baseline value by the 3rd day after discontinuation of phenylbutazone. These results indicate that serum TT4 and FT4 should not be used to evaluate thyroid function in horses receiving phenylbutazone. In addition, results should be interpreted cautiously when phenylbutazone has been administered within 2 days (for FT4) or within 10 days (for TT4) of sample collection.  相似文献   

8.
REASONS FOR PERFORMING STUDY: Endotoxaemia causes a disruption of gastrointestinal motility in the horse but there is no information on its effects on gastric secretion. Lipopolysaccharide (LPS) administration is known to affect gastric secretion in other species. HYPOTHESIS: That LPS, a toxic component of Gram-negative bacteria, would reduce gastric acid secretion and that pretreatment with phenylbutazone (PBZ) would block the effects of LPS. METHODS: The effects of LPS and PBZ on gastric contents were investigated in fasted, mature horses, with permanent gastric cannulae. Horses were pretreated with either saline or PBZ 15 mins before a 60 min infusion of either LPS or saline. Gastric contents were collected at 15 min intervals for 3 h, beginning 15 mins after the start of the LPS or saline infusion. RESULTS: Lipopolysaccharide significantly decreased gastric acid output, [K+] and potassium output and increased [Na+] and sodium output. Phenylbutazone did not affect basal gastric acid secretion but decreased LPS-induced changes in the secreted volume, [Na+] and sodium output. CONCLUSIONS: This study provides evidence that LPS affects gastric acid secretion in the horse and that these LPS-induced changes are mediated, in part, by prostaglandins. POTENTIAL RELEVANCE: Lipopolysaccharide administration can induce changes in the composition of gastric contents in the horse but further work is needed to determine the source of these changes.  相似文献   

9.
Four adult, lactating dairy cows were subjected to diversion (loss) of gastric contents through a T-shaped cannula placed in the cranial part of the duodenum just distal to the pylorus. Diversion was continued for 10 to 12 hours, at which point the cows were very weak and depressed. The volume of effluent during this period ranged from 37.3 to 46.8 L, with the largest volume being produced during the first four hours. All cows became dehydrated, with mean packed cell volume and total plasma protein concentration increasing 30% and 19.6%, respectively, but with only a slight increase in plasma creatinine concentration. Plasma Cl- concentrations decreased from a mean of 97.3 mEq/L at the beginning of diversion to a mean of 87.2 mEq/L at eight hours. This was followed by a plateau or slight increase in concentrations over the final hours of diversion. Plasma K+ concentration followed a similar pattern, decreasing from a mean of 3.9 mEq/L to a mean of 2.94 mEq/L at six hours, followed by increasing values until termination of diversion. No changes in plasma Na+ concentration were noted, except for a mild decrease in one cow. Plasma calcium concentrations decreased significantly, reaching 6.6 +/- 0.6 mEq/L at the end of diversion. Venous pH, plasma HCO3- concentration, and plasma base excess concentration increased during the first four to eight hours of diversion, followed by a gradual decline. Although a mild hypochloremic metabolic alkalosis resulted from diversion of abomasal outflow in all cows, substantiated by a mild increase in plasma strong ion difference, the changes observed were not as great as expected.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
A pilot study in two ponies showed that the plasma concentrations of intramuscularly administered procaine penicillin were higher if phenylbutazone was administered concurrently. In two other trials, each involving five horses, intravenous sodium penicillin was administered with and without concurrent intravenously injected phenylbutazone, and procaine penicillin was injected intramuscularly with and without oral phenylbutazone. In both cases the plasma concentrations of penicillin were higher when phenylbutazone was given. The pharmacokinetic parameters indicated that the effect was probably due to a lower peripheral distribution because the penetration of penicillin into the tissues was greatly reduced.  相似文献   

11.
The purpose of this study was to characterize the pharmacokinetics of a subcutaneously implanted tissue-chamber model. Thermoplastic tissue chambers were implanted in the paralumbar fossae of six steers. Starting 30 days after implantation, the distribution of intravenously administered antipyrine and phenylbutazone into the tissue chambers was studied. These pharmacokinetic experiments were repeated 10 days later to determine the effect of time after implantation on tissue-chamber distribution. Fifty days after implantation, tissue chambers were drained of transudate, refilled with sterile saline and the rate of influx of endogenous urea, creatinine and albumin was measured. Delayed diffusion of antipyrine and phenylbutazone into tissue chambers was well described using a compartmental model in which tissue-chamber fluid represented the third of three compartments arranged in series. The distribution of antipyrine into tissue chambers was greater than that of phenylbutazone; an observation which is well correlated with the high degree of protein binding of phenylbutazone. There was no effect of time on the penetration of the two agents. Rapid diffusion of urea and creatinine and extremely slow influx of albumin into chambers showed that these chambers formed true interstitial compartments.  相似文献   

12.
Rats heavily infected with larval Taenia taeniaeformis show hyperplasia of the gastric mucosa accompanied by mucous cell proliferation, increase in the level of intragastric pH and hypergastrinemia. Sixty one rats were divided into 2 groups designed as infected (36 rats) and control (25 rats) group. These rats were examined with time course of the infection histopathologically and physiopathologically, during 14-112 days postinfection (DPI). In the infected rats, gastric mucosal hyperplasia began to be observed at 56 DPI, and the structural disturbance of zymogenic units in the corpus and mucous units in the antrum had increased with time. However, the degree of these changes in the antrum was weaker than those in the corpus. Alcianblue and/or PAS-positive cells increased in their numbers with time, and 4 types of cells other than typical surface mucous cell and mucous neck cell were observed by electron-microscopy. However, zymogenic and parietal cells decreased in their number after 56 DPI. Further, the infected rats showed changes in the serum concentration of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, glucose and total protein. Some similarities with Menetrier's disease were discussed.  相似文献   

13.
Adrenal and/or thyroid gland function tests were evaluated in horses at various times during short-term therapy with phenylbutazone, stanozolol, and boldenone undecylenate. There were no significant treatment or time effects on mean basal plasma cortisol concentrations in horses during treatment with the following: phenylbutazone, given twice daily (4 to 5 mg/kg, IV) for 5 days; stanozolol, given twice weekly (0.55 mg/kg, IM) for 12 days; boldenone undecylenate, given twice weekly (1.1 mg/kg, IM) for 12 days; or nothing. There was no significant effect of phenylbutazone treatment on the changes in plasma cortisol concentration during the combined dexamethasone-suppression adrenocorticotropic hormone (ACTH)-stimulation test. Plasma cortisol concentration was significantly decreased from base line at 3 hours after dexamethasone administration and was significantly increased from base line at 2 hours after ACTH in all horses (P less than 0.05). Likewise, the stimulation of basal plasma cortisol concentrations at 2 hours after administration of ACTH (P less than 0.05) was not affected by treatment with stanozolol or boldenone undecylenate. There were no significant treatment effects on mean basal plasma concentrations of thyroxine (T4) or triiodothyronine (T3) among horses during the following treatments: stanozolol, given twice weekly (0.55 mg/kg, IM) for 12 days; boldenone undecylenate, given twice weekly (1.1 mg/kg, IM) for 12 days; or nothing. There was a significant time effect on overall mean basal plasma T4 and T3 concentrations (P less than 0.05): plasma T4 was lower on day 8 than on days 1, 10, and 12; plasma T3 was higher on day 8 than on days 4 and 12.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
The objectives of this study were to determine the effect of phenylbutazone premedication on the pharmacokinetics and urinary excretion of frusemide in horses; and on frusemide-induced changes in urinary electrolyte excretion. Six Standardbred mares were used in a 3-way crossover design. The pharmacokinetics and renal effects of frusemide (1 mg/kg bwt i.v.) were studied with and without phenylbutazone premedication (8.8 mg/kg bwt per os 24 h before, followed by 4.4 mg/kg bwt i.v. 30 min before frusemide administration). A control (saline) treatment was also studied. Administration of frusemide without phenylbutazone led to diuresis, natriuresis, kaliuresis and chloruresis, and altered the ratio of sodium:chloride excretion from 0.4 to 1.0 in the first hour of diuresis. When frusemide and phenylbutazone were administered, sodium and chloride excretion in the first hour were significantly (P<0.05) reduced by 40 and 32%, respectively, when compared to frusemide administrationwithout phenylbutazone. The fractional clearance of sodium and chloride was also significantly reduced. Potassium excretion, potassium fractional clearance and the ratio of sodium to chloride excretion were not affected by administration of phenylbutazone. During peak diuresis, phenylbutazone did not affect the efficiency of frusemide with respect to electrolyte excretion. The plasma disposition of frusemide was not affected by phenylbutazone. However, the renal excretion of frusemide decreased by approximately 25%. We conclude that the decreased urinary excretion of frusemide by phenylbutazone led to an attenuation of frusemide-induced increases in urinary excretion of sodium and chloride. Since the efficiency of frusemide was not affected by phenylbutazone, we conclude that phenylbutazone attenuates the renal excretion of frusemide without inhibiting the intrarenal activity of frusemide in horses.  相似文献   

15.
Two Holstein heifers and a steer fitted with ruminal and duodenal cannulas were used to determine acid-base and electrolyte changes associated with metabolic alkalosis induced by duodenal obstruction. Obstruction was induced distally to the pylorus, but proximally to the common bile duct entrance. Ruminal fluid, blood, and urine samples were obtained before and after obstruction was induced. Duodenal obstruction resulted in increased blood pH, bicarbonate concentration, and base-excess values. Severe hypochloremia and hypokalemia were evident in 48 hours. Serum sodium concentration decreased only slightly. Packed cell volume and serum concentrations of urea nitrogen, creatinine, glucose, and inorganic phosphate increased, whereas calcium concentration showed no change. Renal chloride excretion reached near zero in 24 hours, whereas sodium and potassium excretions decreased in the steer, but were unchanged in the heifers. Urine creatinine concentration increased markedly in the heifers and steers. Acid urine was not evident up to 96 hours. Ruminal fluid pH decreased and chloride concentration increased in the steer, but remained unaffected in the heifers. Duodenal obstruction had no effect on rumen sodium, calcium, and magnesium concentrations, but the potassium concentration increased in the heifers. The degrees of alkalosis and electrolyte changes were greater in the steer than in the heifers.  相似文献   

16.
OBJECTIVE: To describe the pharmacokinetics of phenylbutazone and oxyphenbutazone after IV administration in miniature donkeys. ANIMALS: 6 clinically normal miniature donkeys. PROCEDURE: Blood samples were collected before and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after IV administration of phenylbutazone (4.4 mg/kg of body weight). Serum was analyzed in triplicate by use of high-performance liquid chromatography for determination of phenylbutazone and oxyphenbutazone concentrations. The serum concentration-time curve for each donkey was analyzed separately to estimate model-independent pharmacokinetic variables. RESULTS: Serum concentrations decreased rapidly after IV administration of phenylbutazone, and they reached undetectable concentrations within 4 hours. Values for mean residence time ranged from 0.5 to 3.0 hours (median, 1.1 hour), whereas total body clearance ranged from 4.2 to 7.5 ml/kg/min (mean, 5.8 ml/kg/min). Oxyphenbutazone appeared rapidly in the serum; time to peak concentration ranged from 13 to 41 minutes (mean, 26.4 minutes), and peak concentration in serum ranged from 2.8 to 4.0 mg/ml (mean, 3.5 microg/ml). CONCLUSION AND CLINICAL RELEVANCE: Clearance of phenylbutazone in miniature donkeys after injection of a single dose (4.4 mg/kg, IV) is rapid. Compared with horses, miniature donkeys may require more frequent administration of phenylbutazone to achieve therapeutic efficacy.  相似文献   

17.
Five clinically health goats were injected with sulfadimethoxine and sulfadimethyloxazole in a single dose of 100 mg/kg b. wt. by intravenous route. Highest concentration levels of sulfadimethoxine and sulfadimethyloxazole in rumen were detected 1 hour following intravenous injection, then the concentration for both compounds declined at 12 and 8 hours post administration, respectively. In addition, both types of sulfonamide completely disappeared in ruminal fluid samples taken after 24 and 12 hours, respectively. The rate of acetylation for sulfadimethoxine and sulfadimethyloxazole were nearly similar and occurred to a high extent in ruminal fluid (22.95 and 23.72%, respectively). On the other hand, both tested drugs increased significantly the ruminal gas production from the first to eight hours after i.v. injection in goats. Changes in the serum enzyme activities (SGOT, SGPT and alkaline phosphatase) observed with sulfadimethoxine and sulfadimethyloxazole, and represented by a significant decrease in the activity of SGOT and SGPT level, alkaline phosphatase 4 hours sulfadimethoxine and in GOT/GPT ratio 24 and 48 hours after i.v. injection, respectively. The creatinine clearance was significantly decreased after 4 hours following the i.v. administration of sulfadimethoxine and sulfadimethyloxazole in goats.  相似文献   

18.
Primidone, phenytoin, or phenytoin and primidone in combination were given to healthy Beagle dogs for 6 months. Serum biochemical changes in dogs given primidone alone or phenytoin and primidone in combination for the entire 6-month test period included increased activities of alanine aminotransferase, alkaline phosphatase (AP), and gamma-glutamyltransferase, and decreased concentrations of albumin and cholesterol. Changes in dogs given phenytoin alone were limited to increased AP activity and decreased albumin concentration. Sulfobromophthalein excretion and conjugated bile acid concentration were within normal limits. All dogs given primidone alone or phenytoin alone remained clinically healthy throughout the treatment period. Three of 8 dogs given both drugs in combination became clinically ill after 9, 14, and 15 weeks of treatment, and were euthanatized. Two of the dogs developed clinical jaundice. In addition to the serum biochemical abnormalities observed in clinically healthy dogs, these dogs developed hyperbilirubinemia, delayed sulfobromophthalein excretion, and increased conjugated bile acid concentrations. Histologic examination of the liver showed intracanalicular casts of bile pigment typical of intrahepatic cholestasis in all 3 dogs. Histologic findings characteristic of treated dogs included hepatocellular hypertrophy attributable to hyperplasia of the smooth endoplasmic reticulum. Single-cell necrosis and multifocal lipidosis were observed in individuals of all treatment groups. Electron microscopy of the liver showed dilated bile canaliculi and damaged sinusoidal epithelium in dogs given both drugs. The elevated serum AP activity, associated with anticonvulsant drug therapy, was found to be exclusively the liver isoenzyme by cellulose acetate electrophoresis. The hepatic AP was localized to primarily the canalicular membranes by enzyme histochemistry. There was a statistically significant positive correlation between the AP activities of liver and serum. The results of this study indicate that long-term administration of anticonvulsant drugs to dogs is associated with clinical, serum biochemical, and histologic evidence of hepatic dysfunction. High drug dosage contributed most to abnormal serum biochemical test results, and combining phenytoin with primidone was responsible for more severe electron microscopic lesions of the liver of surviving dogs and for the death of 3 dogs.  相似文献   

19.
选用40只4周龄清洁级Wistar大鼠预饲1周后随机均分为4组,即对照组（C组）、低剂量组（L组）、中剂量组（M组）和高剂量组（H组）。分别于饮水中添加0,64．18,128．36,256．72mg／kg的A1C13,建立亚慢性铝暴露大鼠模型。于试验120d处死大鼠,全自动生化分析仪检测血清中尿素氮（BUN）、尿酸（UA）、肌酐（Cr）以及尿液中肌酐（Cr）、尿总蛋白（TP）含量,并计算24h肌酐清除率。结果显示：染铝大鼠血清BUN和UA水平高于C组,且随染铝剂量增加呈升高趋势,但无统计学意义;24h肌酐清除率低于C组,TP含量高于C组（P〈0．05,P〈0．01）,且存在剂量-效应关系。结果说明,亚慢性铝暴露可致大鼠早期肾功能损伤。  相似文献   

20.
Endogenous creatinine clearance and renal excretion of phenylbutazone, osmotically active material, and compounds contributing to the urinary refractive index were studied in 12 Thoroughbred mares after no treatment, after water administration, or after furosemide administration. Urine was quantitatively collected, using urinary bladder catheters. On average, urine flow of the mares was 9 microliters/min/kg without treatment and increased to about 50 microliters/min/kg after water administration and to about 70 microliters/min/kg after furosemide administration. Water administration increased creatinine clearance values and excretion of phenylbutazone. Furosemide administration increased urinary excretion of osmotically active compounds and compounds contributing to urinary refractive index and decreased excretion of phenylbutazone.  相似文献   

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