Pharmacokinetics of the opioid antagonist N-methylnaltrexone and evaluation of its effects on gastrointestinal tract function in horses treated or not treated with morphine

OBJECTIVE: To determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine. ANIMALS: 5 healthy adult horses. PROCEDURES: Horses were treated with MNTX (1 mg/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphine, MNTX (0.75 mg/kg, IV, q 12 hours) and morphine (0.5 mg/kg, IV, q 12 hours) were administered for 6 days. Gastrointestinal variables evaluated were defecation frequency, weight of feces produced, fecal moisture content, intestinal transit time, and borborygmus scores. RESULTS: The time-concentration data for MNTX disposition best fit a 2-compartment model with a steady-state volume of distribution of 244.6 +/- 21.8 mL/kg, t1/2 of 47.04 +/- 11.65 minutes, and clearance of 11.43 +/- 1.06 mL/min/kg. Adverse effects were not observed at doses 相似文献   

Evaluation of Continuous Infusion of Lidocaine on Gastrointestinal Tract Function in Normal Horses

Objective— To determine the effect of continuous infusion of lidocaine on fecal transit time in normal horses.
Study Design— Experimental randomized cross-over study.
Animals— Healthy horses (n=6).
Methods— Barium-filled microspheres were administered to horses by nasogastric intubation and feces were collected every 2 hours for 4 days. A bolus of 2% lidocaine (1.3 mg/kg) was administered randomly, followed by a continuous infusion of lidocaine (0.05 mg/kg/min) for 3 days or an equivalent volume of saline. The washout period was 10 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (number of microspheres observed on radiographs), fecal moisture content, borborygmus score, heart and respiratory rate, and signs of lidocaine toxicity (e.g., ataxia, CNS depression).
Results— During the first 24 hours of lidocaine administration, mean (±SD) fecal output (10.8±6.9 kg) was decreased compared with controls (15±4.9 kg). Mean (±SEM) time for passing 50% of the barium-filled microspheres was shorter in controls (42±1.13 hours) compared with the lidocaine group (50±1.32 hours).
Conclusions— Continuous infusion of lidocaine increases the transit time of feces in normal horses.
Clinical Relevance— Clinicians need to be aware of the effects of using a continuous infusion of lidocaine on the transit time of feces in normal horses, with a potential for exacerbating those effects when combined with drugs that decrease motility and in horses with medical colic (e.g., impaction) or where a diagnosis has not been made.     

Comparison of the effects of intragastric infusions of equal volumes of water, dioctyl sodium sulfosuccinate, and magnesium sulfate on fecal composition and output in clinically normal horses.

A Latin square design was used to compare the effects of laxatives and a corresponding volume of water on gastrointestinal tract function in 4 healthy horses. Horses were intragastrically infused with each of the following: dioctyl sodium sulfosuccinate (DSS; 50 mg/kg of body weight); magnesium sulfate (0.5 g/kg--low dosage); magnesium sulfate (1.0 g/kg--high dosage); and an equal volume of water (6 L) given as a control infusion. From 5 to 33 hours after the high dosage of magnesium sulfate, feces were slightly softer than usual in all horses. In 1 horse, DSS caused mild colic, hyperpnea, and diarrhea from 0.3 to 3 hours after administration. After all laxative treatments and the control infusion, fecal output, fecal water, number of defecations, and fecal water percentage were greater during the first 6 and 12 hours, compared with each subsequent 6-hour period (P less than 0.05). The high dosage of magnesium sulfate had greater effect on fecal output and fecal water than did the low dosage and control infusion (P less than 0.05). However, this effect preceded arrival of the liquid transit marker, polyethylene glycol, and magnesium at their highest concentrations in feces by 12 to 18 hours. Compared with the control infusion, none of the laxative treatments affected excretion of polyethylene glycol and plastic particulate markers, nor did they increase water consumption. It was concluded that the response to intragastric infusions may involve reflex mechanisms in the gastrointestinal tract and that these responses could be used for treatment of colon impactions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of feeding large amounts of grain on colonic contents and feces in horses

OBJECTIVE: To assess changes in systemic hydration, concentrations of plasma electrolytes, hydration and physical properties of colonic contents and feces, and gastrointestinal transit in horses with access to large amounts of grain. ANIMALS: 6 horses with right dorsal colon (RDC) fistulas. PROCEDURE: In a crossover design, horses were alternately fed 1 of 3 diets: orchard grass hay ad libitum after being adapted to this diet for at least 5 days, orchard grass hay ad libitum and 4.55 kg of grain offered every 12 hours after being adapted to orchard grass hay ad libitum for at least 5 days, or orchard grass hay ad libitum and 4.55 kg of grain offered every 12 hours after being adapted to this diet for at least 5 days. Physical examinations were performed and samples of blood, colonic contents, and feces were collected every 6 hours during a 48-hour observation period. RESULTS: Grain ingestion had several effects, including changes in the concentrations of electrolytes in plasma; RDC contents became more homogenous, dehydrated, foamy, and less dense; RDC contents flowed spontaneously when the cannula was opened; RDC contents expanded when heated in an oven; and feces became fetid and less formed. Horses did not have any clinical signs of colic, endotoxemia, or laminitis. CONCLUSIONS AND CLINICAL RELEVANCE: Changes observed in the colonic contents and feces may be explained by the large amounts of hydrolyzable carbohydrates provided by grain. Access to large amounts of grain may increase the risk of tympany and displacement of the large intestine.     

Influence of morphine sulfate on the halothane sparing effect of xylazine hydrochloride in horses

OBJECTIVE: To quantitate the dose and time-related effects of morphine sulfate on the anesthetic sparing effect of xylazine hydrochloride in halothane-anesthetized horses and determine the associated plasma xylazine and morphine concentration-time profiles. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of halothane in O2 and characterize the anesthetic sparing effect (ie, decrease in MAC of halothane) by xylazine (0.5 mg/kg, i.v.) administration followed immediately by i.v. administration of saline (0.9% NaCI) solution, low-dose morphine (0.1 mg/kg), or high-dose morphine (0.2 mg/kg). Selected parameters of cardiopulmonary function were also determined over time to verify consistency of conditions. RESULTS: Mean (+/- SEM) MAC of halothane was 1.05 +/- 0.02% and was decreased by 20.1 +/- 6.6% at 49 +/- 2 minutes following xylazine administration. The amount of MAC reduction in response to xylazine was time dependent. Addition of morphine to xylazine administration did not contribute further to the xylazine-induced decrease in MAC (reductions of 21.9 +/- 1.2 and 20.7 +/- 1.5% at 43 +/- 4 and 40 +/- 4 minutes following xylazine-morphine treatments for low- and high-dose morphine, respectively). Overall, cardiovascular and respiratory values varied little among treatments. Kinetic parameters describing plasma concentration-time curves for xylazine were not altered by the concurrent administration of morphine. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine decreases the anesthetic requirement for halothane in horses. Concurrent morphine administration to anesthetized horses does not alter the anesthetic sparing effect of xylazine or its plasma concentration-time profile.     

Effects of enteral and intravenous fluid therapy, magnesium sulfate, and sodium sulfate on colonic contents and feces in horses

OBJECTIVE: To assess changes in systemic hydration, concentrations of electrolytes in plasma, hydration of colonic contents and feces, and gastrointestinal transit in horses treated with IV fluid therapy or enteral administration of magnesium sulfate (MgSO4), sodium sulfate (NaSO4), water, or a balanced electrolyte solution. ANIMALS: 7 horses with fistulas in the right dorsal colon (RDC). PROCEDURE: In a crossover design, horses alternately received 1 of 6 treatments: no treatment (control); IV fluid therapy with lactated Ringer's solution; or enteral administration of MgSO4, Na2SO4, water, or a balanced electrolyte solution via nasogastric intubation. Physical examinations were performed and samples of blood, RDC contents, and feces were collected every 6 hours during the 48 hour-observation period. Horses were muzzled for the initial 24 hours but had access to water ad libitum. Horses had access to hay, salt, and water ad libitum for the last 24 hours. RESULTS: Enteral administration of a balanced electrolyte solution and Na2SO4 were the best treatments for promoting hydration of RDC contents, followed by water. Sodium sulfate was the best treatment for promoting fecal hydration, followed by MgSO4 and the balanced electrolyte solution. Sodium sulfate caused hypocalcemia and hypernatremia, and water caused hyponatremia. CONCLUSIONS AND CLINICAL RELEVANCE: Enteral administration of a balanced electrolyte solution promoted hydration of RDC contents and may be useful in horses with large colon impactions. Enteral administration of either Na2SO4 or water may promote hydration of RDC contents but can cause severe electrolyte imbalances.     

Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses

OBJECTIVE: To determine an infusion rate of butorphanol tartrate in horses that would maintain therapeutic plasma drug concentrations while minimizing development of adverse behavioral and gastrointestinal tract effects. ANIMALS: 10 healthy adult horses. PROCEDURE: Plasma butorphanol concentrations were determined by use of high-performance liquid chromatography following administration of butorphanol by single IV injection (0.1 to 0.13 mg/kg of body weight) or continuous IV infusion (loading dose, 17.8 microg/kg; infusion dosage, 23.7 microg/kg/h for 24 hours). Pharmacokinetic variables were calculated, and changes in physical examination data, gastrointestinal tract transit time, and behavior were determined over time. RESULTS: A single IV injection of butorphanol was associated with adverse behavioral and gastrointestinal tract effects including ataxia, decreased borborygmi, and decreased defecation. Elimination half-life of butorphanol was brief (44.37 minutes). Adverse gastrointestinal tract effects were less apparent during continuous 24-hour infusion of butorphanol at a dosage that resulted in a mean plasma concentration of 29 ng/ml, compared with effects after a single IV injection. No adverse behavioral effects were observed during or after continuous infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IV infusion of butorphanol for 24 hours maintained plasma butorphanol concentrations within a range associated with analgesia. Adverse behavioral and gastrointestinal tract effects were minimized during infusion, compared with a single injection of butorphanol. Continuous infusion of butorphanol may be a useful treatment to induce analgesia in horses.     

Systemic effects of a prolonged continuous infusion of ketamine in healthy horses

Background: Ketamine as continuous rate infusion (CRI) provides analgesia in hospitalized horses. Objective: Determine effects of prolonged CRI of ketamine on gastrointestinal transit time, fecal weight, vital parameters, gastrointestinal borborygmi, and behavior scores in healthy adult horses. Animals: Seven adult Thoroughbred or Thoroughbred cross horses, with permanently implanted gastric cannulae. Methods: Nonblinded trial. Random assignment to 1 of 2 crossover designed treatments. Ketamine (0.55 mg/kg IV over 15 minutes followed by 1.2 mg/kg/h) or lactated Ringer's solution (50 mL IV over 15 minutes followed by 0.15 mL/kg/h) treatments. Two hundred 3 × 5 mm plastic beads administered by nasogastric tube before drug administration. Every 2 hours vital parameters, behavior scores recorded, feces collected and weighed, and beads retrieved. Every 6 hours gastrointestinal borborygmi scores recorded. Study terminated upon retrieval of 180 beads (minimum 34 hours) or maximum 96 hours. Nontransit time data analyzed between hours 0 and 34. Results: No significant (P < .05) differences detected between treatments in vital signs or gastrointestinal borborygmi. Significant (P = .002) increase in behavior score during ketamine infusion (0.381) from hours 24–34 compared with placebo (0). Ketamine caused significant delay in passage of 25, 50, and 75% of beads (ketamine = 30.6 ± 5.3, 41.4 ± 8.4, 65.3 ± 13.5 hours versus placebo = 26.8 ± 7.9, 34.3 ± 11.1, 45.8 ± 19.4 hours), and significant (P < .05) decrease in fecal weight from hours 22 (12.6 ± 3.2 versus 14.5 ± 3.8 kg) through 34 (18.5 ± 3.9 versus 12.8 ± 6.4 kg) of infusion. Conclusions and Clinical Importance: Ketamine CRI delayed gastrointestinal transit time in healthy horses without effect on vital parameters.     

Effects of epidural morphine on gastrointestinal transit in unmedicated horses

ObjectiveTo evaluate the effect of epidural morphine on gastrointestinal (GI) motility in horses.Study designRandomly ordered crossover design.AnimalsSix healthy adult horses weighing 585 ± 48 kg (mean ± SD).MethodsHorses were randomly assigned to receive either 0.2 mg kg^?1 morphine or an equal volume (0.04 mL kg^?1) of saline epidurally (the first inter coccygeal space) with 2 weeks between treatments. The horses were stabled, fed a standardized diet and allowed water ad libitum throughout the duration of the study. Radiopaque spheres were administered by stomach tube. Xylazine 0.2 mg kg^?1 intravenously was administered prior to epidural injection. Heart rate, respiratory rate, GI sounds score and behavior score were recorded before drug administration and after epidural injection at 4, 8, 12, 18, 24 hours and every 12 hours thereafter for 6 days. Feces were weighed, radiographed and the number of spheres counted. Data were analyzed using a mixed effect model.ResultsAt no time did horses exhibit signs of colic or show significant differences between treatments regarding heart rate, respiratory rate, GI sounds score, behavior score, or cumulative number of spheres. The concentration of spheres per kg of feces was significantly lower (p < 0.05) for the morphine group at 18 and 24 hours. Using the centroid of the curves (spheres kg^?1 plotted versus time) the average transit time after saline epidural was 38 hours and after morphine it was 43 hours. The weight of feces hour^?1 was significantly lower (p < 0.05) at only 4 and 8 hours after morphine.Conclusions and clinical relevanceEpidural morphine, at a dose of 0.2 mg kg^?1, temporarily reduced GI motility but did not cause ileus or colic in this small group of healthy unfasted horses. Care should be taken when extrapolating these data to situations in which other factors may also affect GI motility.     

Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of anesthesia with isoflurane and halothane in horses undergoing arthroscopic surgery

OBJECTIVE: To compare hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of halothane and isoflurane in horses undergoing arthroscopic surgery. ANIMALS: 8 healthy adult horses. PROCEDURE: Anesthesia was maintained with isoflurane or halothane (crossover study). At 6 intervals during anesthesia and surgery, cardiopulmonary variables and related derived values were recorded. Recovery from anesthesia was assessed; gastrointestinal tract motility was subjectively monitored for 72 hours after anesthesia. Horses were administered chromium, and fecal chromium concentration was used to assess intestinal transit time. Venous blood samples were collected for clinicopathologic analyses before and 2, 24, and 48 hours after anesthesia. RESULTS: Compared with halothane-anesthetized horses, cardiac index, oxygen delivery, and heart rate were higher and systemic vascular resistance was lower in isoflurane-anesthetized horses. Mean arterial blood pressure and the dobutamine dose required to maintain blood pressure were similar for both treatments. Duration and quality of recovery from anesthesia did not differ between treatments, although the recovery periods were somewhat shorter with isoflurane. After isoflurane anesthesia, gastrointestinal motility normalized earlier and intestinal transit time of chromium was shorter than that detected after halothane anesthesia. Compared with isoflurane, halothane was associated with increases in serum aspartate transaminase and glutamate dehydrogenase activities, but there were no other important differences in clinicopathologic variables between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with halothane, isoflurane appears to be associated with better hemodynamic stability during anesthesia, less hepatic and muscle damage, and more rapid return of normal intestinal motility after anesthesia in horses undergoing arthroscopic procedures.     

Intravenous continuous infusion of lidocaine for treatment of equine ileus

OBJECTIVE: To determine if intravenous lidocaine is useful and safe as a treatment for equine ileus. Study DESIGN: Prospective double-blinded placebo-controlled trial. STUDY POPULATION: Horses (n = 32) with a diagnosis of postoperative ileus (POI) or enteritis and that had refluxed >20 L or had been refluxing for >24 hours. METHODS: Refluxing horses were administered lidocaine (1.3 mg/kg intravenously [IV] as a bolus followed by a 0.05 mg/kg/min infusion) or saline (0.9% NaCl) solution placebo for 24 hours. Variables evaluated included volume and duration of reflux, time to 1st fecal passage, signs of pain, analgesic use, heart rate and arrhythmias, respiratory rate, temperature, days of hospitalization, outcome (survival to discharge), and complications. RESULTS: Of the lidocaine-treated horses, 65% (11/17) stopped refluxing within 30 hours (mean+/-SD, 15.2+/-2.4 hours) whereas 27% (4/15) of the saline-treated horses stopped within 30 hours. Fecal passage was significantly correlated with response to treatment; horses that responded to lidocaine passed feces within 16 hours of starting the infusion. Compared with placebo treatment, lidocaine treatment resulted in shorter hospitalization time for survivors, equivalent survival to discharge, no clinically significant changes in physical or laboratory variables, and no difference in the rate of incisional infections, jugular thrombosis, laminitis, or diarrhea. Muscle fasciculations occurred in 3 lidocaine-treated horses (18%). CONCLUSION: IV lidocaine significantly improved the clinical course in refluxing horses with minimal side effects. CLINICAL RELEVANCE: At the infusion rate studied, IV lidocaine is safe and should be considered for the treatment of equine ileus.     

Evaluation of association between body size and large intestinal transit time in healthy dogs

OBJECTIVE: To compare large intestinal transit time (LITT) in dogs of various body sizes and determine whether fecal quality was correlated with LITT. ANIMALS: 6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. PROCEDURE: LITT was calculated as the difference between total (TTT) and orocecal transit time (OCTT). Minimum and mean OCTTs were determined by use of the sulfasalazine-sulfapyridine method. Minimum TTT was estimated by use of chromium and ferric oxide as color markers, and mean TTT was calculated from the recovery from feces of ingested colored plastic beads. Fecal moisture content was determined and fecal consistency was scored during the same period. RESULTS: Large-breed dogs had higher fecal moisture content and more watery fecal consistency. No association between body size and OCTT was detected, but there was a positive correlation between body size and mean TTT. Mean LITT increased significantly with body size, from 9.1 +/- 1.1 hours in Miniature Poodles to 39.4 +/- 1.6 hours for Giant Schnauzers. Significant correlations were detected among mean LITT, mean TTT, and fecal scores, whereas no correlation was observed between fecal moisture content and TTT or LITT. CONCLUSIONS AND CLINICAL RELEVANCE: LITT was correlated with fecal consistency in dogs of various body sizes. Mean LITT can be predicted from values for mean TTT in healthy dogs.     

Efficacy of omeprazole paste for prevention of recurrence of gastric ulcers in horses in race training

OBJECTIVE: To determine whether omeprazole oral paste administered at a dosage of 0.5 or 1 mg/kg (0.23 or 0.45 mg/lb), PO, every 24 hours would effectively prevent the recurrence of gastric ulcers in horses in race training. DESIGN: Prospective study. ANIMALS: 135 horses. PROCEDURES: Horses with gastric ulcers were treated with omeprazole at a dosage of 4 mg/kg (1.8 mg/lb), PO, every 24 hours for 28 days. Horses in the dose selection portion of the study were sham dose treated or received 0.5 or 1 mg of omeprazole/kg, PO, every 24 hours for an additional 28 days. Horses in the dose confirmation portion of the study were sham dose treated or received 1 mg of omeprazole/kg, PO, every 24 hours for an additional 28 days. Gastric ulcers were scored before and after the preventive phase of the study (day 28 to day 56) via gastroscopy, and ulcer scores were compared. RESULTS: Sham-dose-treated horses and horses receiving 0.5 mg of omeprazole/kg had significantly higher ulcer scores than did horses receiving 1 mg of omeprazole/kg. There was a significant difference between the proportion of horses receiving 1 mg of omeprazole/kg (38/48 179%]) that remained ulcer free and the proportion of sham-dose-treated horses (7/44 [16%]) that remained ulcer free. CONCLUSIONS AND CLINICAL RELEVANCE: Omeprazole oral paste administered at a dosage of 1 mg/kg, PO, every 24 hours for 28 days was effective for prevention of recurrence of gastric ulcers in horses in race training.     

Risk factors associated with fecal Salmonella shedding among hospitalized horses with signs of gastrointestinal tract disease

OBJECTIVE: To estimate prevalence of and identify risk factors for fecal Salmonella shedding among hospitalized horses with signs of gastrointestinal tract disease. DESIGN: Cross-sectional study. ANIMALS: 465 hospitalized horses with gastrointestinal tract disease. PROCEDURE: Horses were classified as positive or negative for fecal Salmonella shedding during hospitalization by means of standard aerobic bacteriologic methods. The relationship between investigated exposure factors and fecal Salmonella shedding was examined by means of logistic regression. RESULTS: The overall prevalence of fecal Salmonella shedding was 13%. Salmonella serotype Newport was the most commonly isolated serotype (12/60 [20%]), followed by Anatum (8/60 [13%]), Java (13%), and Saint-paul (13%). Foals with gastrointestinal tract disease were 3.27 times as likely to be shedding Salmonella organisms as were adult horses with gastrointestinal tract disease. Adult horses that had been treated with antimicrobial drugs prior to hospitalization were 3.09 times as likely to be shedding Salmonella organisms as were adult horses that had not been treated with antimicrobial drugs prior to hospitalization. Adult horses that underwent abdominal surgery were 2.09 times as likely to be shedding Salmonella organisms as were adult horses that did not undergo abdominal surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a history of exposure to antimicrobial drugs prior to hospitalization and abdominal surgery during hospitalization were associated with Salmonella shedding in adult horses with gastrointestinal tract disease. Foals with gastrointestinal tract disease were more likely to shed Salmonella organisms than were adult horses with gastrointestinal tract disease.     

Influence of age and body size on gastrointestinal transit time of radiopaque markers in healthy dogs

OBJECTIVE: To compare gastric emptying time, small-intestinal transit time (SITT), and orocecal transit time (OCTT) of radiopaque markers in dogs varying in age and body size and to determine whether fecal variables (ie, consistency and moisture content) are related to gastrointestinal tract transit times in dogs. ANIMALS: 24 eight-week-old female puppies, including 6 Miniature Poodles, 6 Standard Schnauzers, 6 Giant Schnauzers, and 6 Great Danes. PROCEDURE: Gastrointestinal tract transit time experiments were performed at 12, 22, 36, and 60 weeks of age. Dogs were fed 30 small radiopaque markers mixed with a meal. Abdominal radiographs were taken. The time at which 50% of the markers had left the stomach (T50) and the time at which the first marker reached the colon were calculated. Fecal moisture content and scoring on the basis of fecal consistency were recorded during the same periods. RESULTS: Puppies had a shorter mean T50 than adults, and mean OCTT decreased significantly only during growth of large-breed dogs. However mean fecal moisture content significantly increased with age, except in Giant Schnauzers. No effect of body size on T50 was found regardless of age, and no difference was observed between OCTT of small- and large-breed adult dogs. The effect of age on the mean SITT was not significant for any breed. However, a strong positive correlation was recorded between body size and fecal moisture content (r2 = 0.77) or fecal scores (r2 = 0.69) in adult dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Age affects T50 in small- and large-breed dogs and OCTT in large-breed dogs. However, body size does not affect T50 or OCTT. A relationship does not exist between gastrointestinal tract transit time and fecal variables in healthy dogs.     

Clinical and Clinicopathologic Effects of Large Doses of Raw Linseed Oil As Compared to Mineral Oil in Healthy Horses

The clinical and Clinicopathologic effects of raw linseed oil and mineral oil were compared. In a crossover experimental design trial, 6 horses were given either raw linseed oil (2.5 mL/kg body weight) or mineral oil (10 mL/kg body weight), twice, 12 hours apart. Two weeks later, the horses received the opposite treatment. All horses given mineral oil or linseed oil developed nonformed feces by 24 hours of the first administration of oil. Horses treated with mineral oil had formed feces at 48 hours; horses treated with linseed oil developed normally formed feces at 96 to 108 hours. All horses treated with linseed oil had signs of depression and anorexia, and 3 had signs of mild colic. These signs were not observed in horses treated with mineral oil. Concentrations of serum glucose and bilirubin were significantly higher in horses treated with linseed oil when compared with horses treated with mineral oil.     

Effect of diet on gentamicin-induced nephrotoxicosis in horses.

Gentamicin sulfate-induced nephrotoxicosis was compared in 2 groups of horses fed different rations. Four horses were fed only alfalfa hay, and 4 other horses were fed only whole oats. Seven days after initiation of the diet, all horses were given gentamicin IV (5 mg/kg of body weight) every 12 hours for 22 days. Urinary gamma-glutamyl-transferase to urinary creatinine (UGGT:UCr) ratio was calculated daily, and serum concentration of gentamicin was measured at 1 and 12 hours after drug administration. Results indicated that horses fed oats had greater renal tubular damage than did horses fed alfalfa. Mean UGGT:UCr for horses fed alfalfa was 47.1 +/- 18.8 and was 100.0 +/- 19.0 for horses fed oats (P = 0.007). The UGGT:UCr in horses fed oats was greater than 100 for a total of 54 days; horses fed alfalfa had UGGT:UCr greater than 100 for only 7 days. Two horses not given gentamicin were fed only oats and 2 were fed only alfalfa. These horses had mean UGGT:UCr of 17.6 +/- 2.2 and 30.5 +/- 3.0, respectively. Mean peak and trough concentrations of gentamicin were statistically different for horses fed oats and those fed alfalfa (peak 23.16 +/- 1.87 and 14.07 +/- 1.79 micrograms/ml, respectively [P = 0.0001], and trough, 1.81 +/- 0.69 and 0.71 +/- 0.70 micrograms/ml, respectively [P = 0.0270]). Mean half-lives of gentamicin (estimated from peak and trough concentrations) for horses fed alfalfa (2.58 +/- 0.26 hours) and horses fed oats (2.88 +/- 0.27 hours) were not significantly different. Horses fed only oats had greater degree of gentamicin-induced nephrotoxicosis than did those fed only alfalfa.     

Pharmacokinetics of acetazolimide after intravenous and oral administration in horses

OBJECTIVE: To determine the pharmacokinetics of acetazolamide administered IV and orally to horses. ANIMALS: 6 clinically normal adult horses. PROCEDURE: Horses received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and blood samples were collected at regular intervals before and after administration. Samples were assayed for acetazolamide concentration by high-performance liquid chromatography, and concentration-time data were analyzed. RESULTS: After IV administration of acetazolamide, data analysis revealed a median mean residence time of 1.71 +/- 0.90 hours and median total body clearance of 263 +/- 38 ml/kg/h. Median steady-state volume of distribution was 433 +/- 218 ml/kg. After oral administration, mean peak plasma concentration was 1.90 +/- 1.09 microg/ml. Mean time to peak plasma concentration was 1.61 +/- 1.24 hours. Median oral bioavailability was 25 +/- 6%. CONCLUSIONS AND CLINICAL RELEVANCE: Oral pharmacokinetic disposition of acetazolamide in horses was characterized by rapid absorption, low bioavailability, and slower elimination than observed initially after IV administration. Pharmacokinetic data generated by this study should facilitate estimation of appropriate dosages for acetazolamide use in horses with hyperkalemic periodic paralysis.     

Effects of mosapride, a 5-hydroxytryptamine 4 receptor agonist, on electrical activity of the small intestine and cecum in horses

OBJECTIVE: To examine the effects of various doses of mosapride, a 5-hydroxytryptamine 4 receptor agonist, on motility of the small intestine and cecum in horses by use of electrical activity and to determine the dose that provides the optimal response. ANIMAL: 6 healthy adult Thoroughbreds. PROCEDURE: Electrical activity of the small intestine and cecum was recorded before and after mosapride administration by use of an electrogastrograph. Mosapride (0.5, 1, 1.5, and 2 mg/kg) was dissolved in 200 mL of water and administered orally to horses through a nasogastric tube. Three hours after drug administration, mean amplitude of electrical activity calculated for a period of 30 minutes was expressed as the percentage of the mean amplitude of electrical activity for a period of 30 minutes before drug administration. RESULTS: Mosapride administered orally increased the percentage of the mean amplitude of electrical activity in the small intestine and cecum in a dose-dependent manner. Mean +/- SD values differed significantly for 1, 1.5, and 2 mg/kg (127.0 +/- 12.5%, 137.7 +/- 22.2%, and 151.1 +/- 24.0%, respectively) in the small intestine and for 1.5 and 2 mg/kg (130.1 +/- 34.5% and 151.6 +/- 45.2%, respectively) in the cecum. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of this study clearly documents that mosapride promotes motility in the small intestine and cecum of horses and that the optimal orally administered dosage is 1.5 to 2 mg/kg. Therefore, mosapride may be useful for treatment of horses with gastrointestinal tract dysfunction.     

Comparison of ivermectin, oxibendazole, and pyrantel pamoate in suppressing fecal egg output in horses

Thirty resident horses at a boarding stable in Alberta were used to evaluate the relative efficacies of ivermectin, oxibendazole, and pyrantel pamoate in reducing fecal egg output in adult horses under routine management conditions during spring and early summer, and to more clearly define the duration of suppression of fecal egg production following anthelmintic treatment. Horses were blocked according to pretreatment egg counts and randomly assigned to one of three treatments: pyrantel pamoate at 6.6 mg/kg body weight; oxibendazole at 10 mg/kg body weight; or ivermectin at 200 μg/kg body weight. All treatments were administered orally as a paste on day 0.Fecal samples were collected for examination by the modified Wisconsin procedure before treatment, and then at 4-11 day intervals up to day 72.

Very few if any strongyle eggs were found in the feces of any horses up to day 35. On days 42, 50 and 57, the geometric mean egg count for the ivermectin group was significantly (p<0.05) lower than that for the oxibendazole or pyrantel pamoate groups. Based on a survival curve analysis of the data, the mean number of days for recurrence of eggs in the feces was significantly longer for the ivermectin group than for the oxibendazole and pyrantel pamoate groups.

Under conditions encountered in this study, the posttreatment interval to resumption of fecal egg out-put in horses treated with ivermectin was eight to nine weeks, compared with five to six weeks for horses treated with oxibendazole or pyrantel pamoate.