Effects of indwelling nasogastric intubation on gastric emptying of a liquid marker in horses

OBJECTIVE: To determine the effects of indwelling nasogastric intubation on the gastric emptying rate of liquid in horses. ANIMALS: 6 healthy horses. PROCEDURES: Horses were assigned to treatment and control groups in a prospective randomized crossover study with a washout period of at least 4 weeks between trials. Acetaminophen (20 mg/kg) diluted in 1 L of distilled water was administered via nasogastric tube at time points of 0, 12, 30, 48, and 72 hours to evaluate the liquid-phase gastric emptying rate. In control horses, nasogastric tubes were removed after administration of acetaminophen. In horses receiving treatment, the tube was left indwelling and maintained for 72 hours. A 10-mL sample of blood was collected from a jugular vein immediately before and 20, 40, 60, 80, 100, 120, and 180 minutes after acetaminophen administration. Serum acetaminophen concentrations were measured by use of a colorimetric method. RESULTS: Peak serum acetaminophen concentration was significantly higher in the control group (38.11 microg/mL) than in the treatment group (29.09 microg/mL), and the time required to reach peak serum acetaminophen concentration was significantly shorter in the control group (22.79 minutes) than in the treatment group (35.95 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that indwelling nasogastric intubation has a delaying effect on the gastric emptying rate of liquids. Veterinarians should consider the potential for delayed gastric emptying when placing and maintaining an indwelling nasogastric tube for an extended period of time after surgery. Repeated nasogastric intubation may be better than maintenance of an indwelling tube in horses with ileus.     

Yohimbine ameliorates the effects of endotoxin on gastric emptying of the liquid marker acetaminophen in horses.

The effect of yohimbine pretreatment on gastric emptying of a liquid marker in horses was evaluated by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal, fasted horses, in horses given endotoxin (E. coli 055 B5; 0.2 microg/kg) intravenously, and in horses given yohimbine (0.25 mg/kg, IV, over 30 minutes) plus endotoxin. Acetaminophen (20 mg/kg) was given by stomach tube 15 minutes after the endotoxin infusion. Blood samples for acetaminophen analysis were collected, and time to reach the peak serum concentration (Tmax), the maximum serum concentration (Cmax) and the area under the acetaminophen serum concentration versus time curve (AUC) were determined for each treatment group. Endotoxin significantly increased Tmax, indicating a profound delay in gastric emptying and yohimbine pretreatment significantly (P < or = 0.05) prevented this effect.     

Effect of an indwelling nasogastric tube on gastric emptying rates of liquids in horses

OBJECTIVE: To evaluate the effect of an indwelling nasogastric tube on gastric emptying of liquids in horses. ANIMALS: 9 healthy adult horses. PROCEDURE: A randomized block crossover design was used. For treatment group horses, a nasogastric tube was placed and 18 hours later, acetaminophen was administered; the nasogastric tube remained in place until the experiment was complete. For control group horses, a nasogastric tube was passed into t stomach, acetaminophen was administered, and the nasogastric tube was removed immediately. Serial blood samples were collected 15 minutes before and after administration of acetaminophen. Serum concentration of acetaminophen was determined by use of fluorescence polarization immunoassay. The variables, time to maximum acetaminophen concentration (Tmax) and the appearance constant for acetaminophen (Kapp), were determined. The values for Kapp and Tmax in horses with and without prolonged nasogastric tube placement were compared. RESULTS: No significant difference was found in Kapp between horses with and without prolonged nasogastric tube placement; the median difference in Kapp was 0.01 min(-1) (range, -0.48 to 0.80 min(-1). No significant difference was found in Tmax between horses with and without prolonged nasogastric tube placement; the median difference in Tmax was 5 minutes (range, -30 to 50 minutes). Reanalysis of data following the removal of possible outlier values from 1 horse resulted in a significant difference in Tmax between horses with and without prolonged nasogastric tube placement. CONCLUSIONS AND CLINICAL RELEVANCE: Although no clinically important impact of 18 hours of nasogastric intubation was found on gastric emptying in healthy was found among horses.     

Evaluation of acetaminophen absorption in horses with experimentally induced delayed gastric emptying

OBJECTIVE: To evaluate the correlation between the half-time of liquid-phase gastric emptying (T50) determined by use of nuclear scintigraphy, using technetiumTc 99m pentetate, and absorption variables of orally administered acetaminophen in horses with experimentally delayed gastric emptying. ANIMALS: 6 mature horses. PROCEDURE: Delayed gastric emptying was induced by IV injection of atropine sulfate. Twenty minutes later, acetaminophen and technetium Tc 99m pentetate were administered simultaneously via nasogastric tube. Serial lateral images of the stomach region were obtained, using a gamma camera. Power exponential curves were used for estimation of T50 and modified R2 values for estimation of goodness-of-fit of the data. Serial serum samples were obtained, and acetaminophen concentration was determined, using fluorescence polarization immunoassay. Maximum serum concentration (Cmax), time to reach maximum serum concentration (Tmax), area under the curve for 480 minutes, and the appearance rate constant were determined, using a parameter estimation program. Correlations were calculated, using a Spearman rank correlation coefficient. RESULTS: A significant correlation was detected between T50 determined by use of scintigraphy and Tmax determined by use of acetaminophen absorption. Correlation between T50 and other absorption variables of acetaminophen was not significant. CONCLUSIONS AND CLINICAL RELEVANCE: The acetaminophen absorption method was a valid technique in this model of delayed gastric emptying in horses. The method may be a valuable tool for use in research as well as in clinical evaluation of gastric emptying in horses.     

Metoclopramide ameliorates the effects of endotoxin on gastric emptying of acetaminophen in horses.

The effect of metoclopramide on gastric emptying of a liquid marker in horses was evaluated by measuring serum concentrations of acetaminophen. Gastric emptying was determined in normal, fasted horses (n = 7), horses given endotoxin intravenously (n = 7), and horses given intravenous metoclopramide 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 vs time curve (AUC) were compared among treatment groups. Endotoxin caused a profound delay in gastric emptying, and pretreatment with metoclopramide significantly (P < 0.05) ameliorated this effect.     

Effect of orally administered cimetidine and ranitidine on abomasal luminal pH in clinically normal milk-fed calves

OBJECTIVE: To characterize the change of pH in the abomasal lumen throughout a 24-hour period, to determine whether pH of the abomasal body differs from pH of the pyloric antrum, and to determine whether oral administration of cimetidine and ranitidine alters pH of the abomasal lumen in milk-fed calves. ANIMALS: 5 male dairy calves (4 Holsteins-Friesian, 1 Ayrshire), 5 to 15 days old. PROCEDURE: Cannulas were surgically positioned in the abomasal body and pyloric antrum of each calf. Calves received the following treatments in a randomized crossover design: milk replacer (60 ml/kg of body weight, q 12 h [untreated control calves]), milk replacer and cimetidine (50 or 100 mg/kg, q 8 h), or milk replacer and ranitidine (10 or 50 mg/kg, q 8 h). The pH of the abomasal body and pyloric antrum was measured for 24 hours, using miniature glass pH electrodes. RESULTS: Suckling of milk replacer immediately increased abomasal luminal pH from 1.4 to 6.0, followed by a gradual decrease to preprandial values by 6 hours. Preprandial and postprandial pH values were not significantly different between the abomasal body and pyloric antrum, indicating lack of pH compartmentalization in the abomasum of milk-fed calves. Administration of cimetidine and ranitidine caused a significant dose-dependent increase in mean 24-hour abomasal luminal pH. CONCLUSIONS AND CLINICAL RELEVANCE: Abomasal acid secretion in milk-fed calves is mediated in part by histamine type-2 receptors. Cimetidine and ranitidine may be efficacious in the treatment of abomasal ulcers in milk-fed calves.     

The effects of phenylbutazone on the morphology and prostaglandin concentrations of the pyloric mucosa of the equine stomach

Phenylbutazone, a nonsteroidal anti-inflammatory drug known to produce gastric ulcers, was administered intravenously (13.46 mg/kg body weight) daily to 12 horses. Horses were euthanatized daily after 24, 48, 72, and 96 hours following the initial injection. Eight untreated horses served as controls. Small multifocal pyloric erosions were seen after 24 hours and then progressed in severity over time. The erosions were characterized by sloughing of the surface epithelium, subepithelial bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries, and microthrombosis of the capillaries of the pyloric mucosa. Large numbers of neutrophils with abundant fibrin and cellular debris were present at the erosion sites. Eroded pyloric mucosa and adjacent macroscopically intact mucosa were examined ultrastructurally. In both the macroscopically eroded mucosa and multifocally in the adjacent macroscopically uneroded mucosa, there was cellular swelling of the endothelium, pericytes, and smooth muscle cells of arterioles. In capillaries and post-capillary venules, the endothelium ranged from swollen to lysed and necrotic. Extensive extravasation of erythrocytes and edema were seen. These lesions were not seen in the control horses. Phenylbutazone produces a microvascular injury that is associated with the formation of pyloric erosions in horses. The pyloric mucosa of six horses was assayed for prostacyclin and prostaglandin E2 at 48 and 96 hours following the initial injection. There was no statistically significant difference between prostaglandin concentrations in the mucosa of control and treated horses. It was concluded that there was little correlation between pyloric mucosal prostaglandin concentrations and pyloric erosions after 48 hours.     

Prevalence and treatment of gastric ulcers in Thoroughbred racehorses of Korea

BackgroundGastric ulcer is one of the prevalent diseases in racehorses. However, it has not been recognized as important in Korea, and drugs used to treat gastric ulcers are included in the doping test list, so they are not allowed to be administered to racehorses in training.ObjectivesThis study was performed 1) to investigate the prevalence and the severity of gastric ulcers in Thoroughbred racehorses in Korea, 2) to confirm the therapeutic effect of ranitidine and omeprazole, and 3) to compare the efficacy between ranitidine and omeprazole.MethodsForty-nine horses were randomly recruited, and gastroscopy was performed within two days after racing. Twelve horses with a sum grade of five or higher were randomly assigned to two treatment groups. Seven horses were administered ranitidine, and five horses were administered omeprazole. Follow-up gastroscopy was scheduled within one to five days after finishing the treatment.ResultsThe prevalence of gastric ulcer in Korean Thoroughbred racehorses after racing was 100%, and the grade was more severe in the non-glandular region than in the pyloric region. There was no correlation between the severity of gastric ulcer in the two regions. Omeprazole had a greater therapeutic effect than ranitidine.ConclusionsThis study shows the importance of recognizing gastric ulcers as an important factor, and omeprazole as a possible treatment option in Korea, as it has been removed from the list of prohibited substances for racehorses. Thus, the use of omeprazole is currently recommended until one day before the race.     

Phenylbutazone prevents the endotoxin-induced delay in gastric emptying in horses.

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.     

Comparison of nuclear scintigraphy and acetaminophen absorption as a means of studying gastric emptying in horses

OBJECTIVE: To evaluate the correlation between halftime of liquid-phase gastric emptying (T50), determined with nuclear scintigraphy using technetium Tc 99m pentetate, and absorption variables of orally administered acetaminophen. ANIMALS: 6 mature horses. PROCEDURE: Technetium Tc 99m pentetate (10 mCi) and acetaminophen (20 mg/kg of body weight) were administered simultaneously in 200 ml of water. Serial left and right lateral images of the stomach region were obtained with a gamma camera, and T50 determined separately for counts obtained from the left side, the right side and the geometric mean. Power exponential curves were used for estimation of T50 and modified R2 values for estimation of goodness of fit of the data. Serial serum samples were taken, and acetaminophen concentration was determined, using fluorescence polarization immunoassay. Maximum serum concentration (Cmax), time to reach maximum serum concentration (Tmax), area under the curve for 240 minutes and the absorption constant (Ka) were determined, using a parameter estimation program. Correlations were calculated, using the Spearman rank correlation coefficient. RESULTS: Correlations between T50 and Tmax and between T50 and Ka were significant. CONCLUSIONS AND CLINICAL RELEVANCE: Tmax and Ka are valuable variables in the assessment of liquid-phase gastric emptying using acetaminophen absorption. Acetaminophen absorption may be a valuable alternative to nuclear scintigraphy in the determination of gastric emptying rates in equine patients with normally functioning small intestine.     

A rapid and strong laparoscopic-assisted gastropexy in dogs

OBJECTIVE: To develop a technique for laparoscopic gastropexy in dogs and evaluate effects on stomach position and strength of the adhesion between the stomach and abdominal wall. ANIMALS: 8 healthy dogs. PROCEDURE: Dogs were anesthetized, and the abdomen was insufflated with carbon dioxide. A laparoscope was placed through a cannula inserted on the abdominal midline caudal to the umbilicus. Babcock forceps placed through a cannula inserted lateral to the right margin of the rectus abdominus muscle were used to exteriorize the pyloric antrum, a longitudinal incision was made through the serosa and muscular layer of the pyloric antrum, and the seromuscular layer of the pyloric antrum was sutured to the transversus abdominus muscle. After surgery, positive-contrast gastrography was used to evaluate stomach position and the onset of gastric emptying, and ultrasonography was used to assess stomach wall activity and mobility. Dogs were euthanatized 1 month after surgery, and tensile strength of the adhesion was tested. RESULTS: In all dogs, stomach position and the onset of gastric emptying were normal 25 days after surgery, and the pyloric antrum was firmly attached to the abdominal wall 30 days after surgery. Mean +/- SD ultimate load of the adhesion in tension was 106.5 +/- 45.6 N. CONCLUSIONS AND CLINICAL RELEVANCE: The laparoscopic gastropexy technique described in the present study could be performed quickly and easily by an experienced surgeon, resulted in a strong fibrous adhesion between the stomach and abdominal wall, and appeared to cause minimal stress to the dogs.     

Oral pharmacokinetics of acetaminophen to evaluate gastric emptying profiles of Shiba goats

The pharmacokinetics of acetaminophen was investigated following oral dosing to Shiba goats in order to evaluate the properties of gastric emptying. Acetaminophen was intravenously and orally administered at 30 mg/kg body weight to goats using a crossover design with a 3-week washout period. The stability of acetaminophen in rumen juice was also assessed. Acetaminophen concentrations were measured by HPLC. Since acetaminophen was stable in rumen juice for 24 hr, the extremely low bioavailability (16%) was attributed to its hepatic extensive first-pass effect. The mean absorption time and absorption half-life were unexpectedly short (4.93 and 3.35 hr, respectively), indicating its marked absorption from the forestomach, which may have been due to its smaller molecular weight. Therefore, acetaminophen was considered to be unsuitable for evaluating gastric emptying in Shiba goats.     

Retention of acetaminophen in an in vitro model of solid-phase gastric emptying of animals

OBJECTIVE: To apply an in vitro model for assessment of the solid-phase binding capacity of acetaminophen and thus assess the reliability of this marker for evaluation of solid-phase gastric emptying in vivo in animals. SAMPLE POPULATION: 4 test meals. PROCEDURES: A spectrophotometric method for detection of acetaminophen was validated and applied for assessment of the percentage retention of acetaminophen in the solid phase of 4 test meals. The gastric milieu was simulated by incubating each meal in artificial gastric juice for 2 hours in a shaking water bath maintained at 37 degrees C. Solid-phase retention was then assessed 3 times by measuring the amount of acetaminophen that had leached into the liquid phase. RESULTS: Acetaminophen was poorly retained in the solid phase of all the test meals examined in the study. There was also a large degree of variability in the percentage retention for each meal when the experiment was repeated 3 times. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the results of this in vitro study confirmed that acetaminophen may not be an appropriate marker of solid-phase gastric emptying. The acetaminophen gastric emptying test should be applied only for the assessment of liquid-phase emptying in animals.     

The prokinetic effect of mosapride citrate on horse gastric emptying rates

The prokinetic effect of the 5-HT4 receptor agonist mosapride was evaluated in seven healthy thoroughbreds. Mosapride was orally administered at doses of 0.5, 1.0 or 1.5 mg/kg. The breath 13CO2/12CO2 rate (Delta13CO2), an indirect indicator for the rate of gastric emptying, was measured at appropriate points for 4 hr after drug administration. There was a significant increase compared with the control value at 15, 20 and 165 min for 0.5 mg/kg, 30 min at 1.0 mg/kg and 165 min for 1.5 mg/kg. The results suggest that mosapride may facilitate the gastric emptying in horses.     

Evaluation of canine gastric motility with ultrasonography

For the evaluation of canine gastric motility with ultrasonography, contraction number of pyloric antrum and gastric emptying time (GET) by area and volume method developed by Bolondi et al.'s method were studied in 14 dogs. All experimental dogs were administered with saline and soup solution (10 ml/kg, B.W.). The mean values of contraction number of pyloric antrum in saline and soup group were 4.19 +/- 1.30/min and 4.82 +/- 0.65/min before feeding, and overall mean values were 4.66 +/- 1.37/min and 5.13 +/- 1.71/min, respectively. The mean values of the GET by area and volume method were 36.73 +/- 11.27, 40.00 +/- 8.87 min in saline group and 61.35 +/- 17.58, 59.11 +/- 14.46 min in soup group. In the GET in saline and soup groups, there was no significant difference between the area and volume method (p>0.05). Therefore, Bolondi et al.'s method by ultrasound can be used to evaluate the antropyloric motility and gastric emptying time with area and volume methods. The area method is easier to determine the GET than the volume method, but the latter is more accurate.     

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.     

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 the effects of the opioid agonist morphine on gastrointestinal tract function in horses

OBJECTIVE: To evaluate the effects of morphine administration for 6 days on gastrointestinal tract function in healthy adult horses. ANIMALS: 5 horses. PROCEDURES: Horses were randomly allocated into 2 groups in a crossover study. Horses in the treatment group received morphine sulfate at a dosage of 0.5 mg/kg, IV, every 12 hours for 6 days. Horses in the control group received saline (0.9% NaCl) solution at a dosage of 10 mL, IV, every 12 hours for 6 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (evaluated by use of barium-filled spheres and radiographic detection in feces), fecal moisture content, borborygmus score, and signs of CNS excitement and colic. RESULTS: Administration of morphine resulted in gastrointestinal tract dysfunction for 6 hours after each injection. During those 6 hours, mean +/- SD defecation frequency decreased from 3.1 +/- 1 bowel movements in control horses to 0.9 +/- 0.5 bowel movements in treated horses, weight of feces decreased from 4.1 +/- 0.7 kg to 1.1 +/- 0.7 kg, fecal moisture content decreased from 76 +/- 2.7% to 73.5 +/- 2.9%, and borborygmus score decreased from 13.2 +/- 2.9 to 6.3 +/- 3.9. Mean gastrointestinal transit time was also increased, compared with transit times in control horses. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine administered at 0.5 mg/kg twice daily decreased propulsive motility and moisture content in the gastrointestinal tract lumen. These effects may predispose treated horses to development of ileus and constipation.     

Effect of erythromycin and gentamicin on abomasal emptying rate in suckling calves

BACKGROUND: Commonly used dosage protocols for antimicrobial agents may alter the rate of gastric emptying. HYPOTHESIS: Parenteral administration of erythromycin increases and gentamicin decreases the rate of abomasal emptying. ANIMALS: Five male Holstein-Friesian calves (8-15 days of age). METHODS: Calves received each of the following 4 IM treatments in random order: control, 2 mL of 0.9% NaCl; erythromycin, 8.8 mg/kg; low-dose gentamicin, 4.4 mg/kg; high-dose gentamicin, 6.6 mg/kg. Abomasal emptying rate was assessed by acetaminophen and glucose absorption. Calves were fed 2 L of cow's milk containing acetaminophen (50 mg/kg body weight) 30 minutes after each treatment was administered, and jugular venous blood samples were obtained periodically after suckling. The maximum observed plasma acetaminophen concentration (actual C(max)) and time of actual C(max) (actual T(max)) were determined, and pharmacokinetic modeling was used to calculate model C(max) and model T(max). RESULTS: Erythromycin increased abomasal emptying rate, as indicated by a shorter time to actual T(max) and model T(max) (P < .05). Abomasal emptying rate after injection of low-dose gentamicin was similar to that of control. Administration of high-dose gentamicin resulted in a longer time to actual T(max) (P= .021) but did not change model T(max) (P= .62). CONCLUSIONS AND CLINICAL RELEVANCE: IM injection of erythromycin increased abomasal emptying rate in dairy calves, whereas low-dose and high-dose gentamicin did not alter the rate of abomasal emptying as measured by acetaminophen kinetics and glucose absorption. The clinical relevance of these findings remains to be determined.     

Pharmacokinetics of voriconazole after oral and intravenous administration to horses

OBJECTIVE: To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. ANIMALS: 6 adult horses. PROCEDURES: Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. RESULTS: Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 +/- 18.41%. The elimination half-life after a single orally administered dose was 13.11 +/- 2.85 hours, and the maximum plasma concentration was 2.43 +/- 0.4 microg/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration 相似文献