Pharmacokinetics and pharmacodynamics of furosemide after oral administration to horses

Furosemide is the most common diuretic drug used in horses. Furosemide is routinely administered as IV or IM bolus doses 3-4 times a day. Administration PO is often suggested as an alternative, even though documentation of absorption and efficacy in horses is lacking. This study was carried out in a randomized, crossover design and compared 8-hour urine volume among control horses that received placebo, horses that received furosemide at 1 mg/kg PO, and horses that received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma furosemide concentrations, PCV, and total solids were obtained at specific time points from treated horses. Furosemide concentrations were determined by reversed-phase high-performance liquid chromatography with fluorescent detection. Systemic availability of furosemide PO was poor, erratic, and variable among horses. Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5, 9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over the 8-hour period. The maximum plasma concentration of 0.03 microg/mL after administration PO was not sufficient to increase urine volume compared with control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a mild decrease in urine specific gravity within 1-2 hours after administration of furosemide PO, and urine specific gravity was significantly lower in horses treated with furosemide PO compared with control horses at the 2-hour time point. Systemic availability of furosemide PO was poor and variable. Furosemide at 1 mg/kg PO did not induce diuresis in horses.     

Effects of alpha2-adrenergic receptor agonists on urine production in horses deprived of food and water

OBJECTIVE: To quantitate the dose- and time-related effects of IV administration of xylazine and detomidine on urine characteristics in horses deprived of feed and water. ANIMALS: 6 horses. PROCEDURE: Feed and water were withheld for 24 hours followed by i.v. administration of saline (0.9% NaCI) solution, xylazine (0.5 or 1.0 mg/kg), or detomidine (0.03 mg/kg). Horses were treated 4 times, each time with a different protocol. Following treatment, urine and blood samples were obtained at 15, 30, 60, 120, and 180 minutes. Blood samples were analyzed for PCV and serum concentrations of total plasma solids, sodium, and potassium. Urine samples were analyzed for pH and concentrations of glucose, proteins, sodium, and potassium. RESULTS: Baseline (before treatment) urine flow was 0.30 +/- 0.03 mL/kg/h and did not significantly change after treatment with saline solution and low-dose xylazine but transiently increased by 1 hour after treatment with high-dose xylazine or detomidine. Total urine output at 2 hours following treatment was 312 +/- 101 mL versus 4,845 +/- 272 mL for saline solution and detomidine, respectively. Absolute values of urine concentrations of sodium and potassium also variably increased following xylazine and detomidine administration. CONCLUSIONS AND CLINICAL RELEVANCE: Xylazine and detomidine administration in horses deprived of feed and water causes transient increases in urine volume and loss of sodium and potassium. Increase in urine flow is directly related to dose and type of alpha2-adrenergic receptor agonist. Dehydration in horses may be exacerbated by concurrent administration of alpha2-adrenergic receptor agonists.     

Clinical, biochemical, and hygiene assessment of stabled horses provided continuous or intermittent access to drinking water

OBJECTIVE: To compare health, hydration status, and management of stabled pregnant mares provided drinking water continuously or via 1 of 3 intermittent delivery systems. ANIMALS: 22 Quarter Horse (QH) or QH-crossbred mares and 18 Belgian or Belgian-crossbred mares (study 1); 24 QH or QH-crossbred mares and 18 Belgian or Belgian-crossbred mares (study 2). PROCEDURE: Stabled horses were provided water continuously or via 1 of 3 intermittent water delivery systems in 2 study periods during a 2-year period. Body temperature, attitude, appetite, water intake, and urine output were recorded daily. Hygiene of each horse and the stable were assessed weekly. Clinical and biochemical measures of hydration were determined 3 times during each study. Clinical measures of hydration included skin turgor, gum moisture, capillary refill time, and fecal consistency. Biochemical measures of hydration included PCV, plasma total protein concentration, serum osmolality, plasma vasopressin concentration, urine specific gravity, and urine osmolality. RESULTS: All horses remained healthy. Stable hygiene was worse when horses had continuous access to water. Clinical and biochemical measures of hydration did not differ among water delivery systems. CONCLUSIONS AND CLINICAL RELEVANCE: Various continuous and intermittent water delivery systems provided adequate amounts of water to stabled horses to maintain health and hydration status. Providing intermittent access to water may be preferable on the basis of stable hygiene.     

Responses of horses to a water deprivation test

An investigation was made to determine the effects of water deprivation induced dehydration on changes in urine specific gravity (Usg) and urine osmolality (Uosm) in 6 horses with normal renal function. In addition, the effects of dehydration on serum and urine urea nitrogen, creatinine and various electrolytes as well as the effects of dehydration on acid-base status were studied.Following water deprivation sufficient to produce 12–15% decrease in body weight, 95% of the normal horses should have a Usg of at least 1.042, a Uosm of 1310 mOsmg/kg and a urine osmolality/serum osmolality ratio of 4.14.After 72 hours of water deprivation, the mean weight loss was 13.5% of previous body weight. Serum and urine urea nitrogen concentrations increased by 68% and 130%, respectively, while plasma sodium and chloride concentrations increased by 10% and 14%, respectively. In contrast, urine chloride and calcium concentrations decreased by 90.8% and 52.5%, respectively. There was little change in plasma potassium, phosphorus or calcium concentrations. Urine sodium and potassium concentrations increased initially but were near normal after 72 hours of water deprivation. Azotemia developed and was considered to be of extrarenal origin on the basis of normal routine urinalysis and renal clearance ratio of sodium.     

Influence of furosemide treatment on fluid and electrolyte balance in horses

Alterations in electrolyte and acid-base balance were studied in 6 horses for 8 hours after furosemide administration (1 mg/kg of body weight, IM), and the results were compared with those for 5 healthy untreated horses (controls) kept under identical environmental conditions. In the treated group, decreases in plasma potassium, chloride, and calcium concentrations and increases in total plasma protein content persisted for the 8-hour observation period, whereas there was no change in plasma sodium concentration, osmolality, or packed cell volume. Plasma bicarbonate concentration and PCO2 remained high throughout the study, during which time venous blood pH was modestly increased only at the 6-hour sampling time. Furosemide treatment resulted in decreases in urine pH, specific gravity, osmolality, and potassium and calcium concentrations and increases in urine volume and total urine sodium, chloride, and calcium excretion. Body weight decreased 19.2 +/- 5.2 kg (mean +/- SD) in treated horses (4 +/- 1% of body weight), compared with a weight loss of 8 +/- 2.1 kg in untreated horses (1.5 +/- 0.4% of body weight) during the 8-hour experimental period. The increased fluid losses induced by the diuretic did not cause any obvious clinical signs in the horses. Pulse pressure, skin turgor, capillary refill time, and jugular distensibility remained unchanged throughout the experimental period.     

Effect of oral administration of electrolyte pastes on rehydration of horses

OBJECTIVE: To determine whether the composition of electrolyte pastes formulated for oral administration influences voluntary water intake (WI) by horses recovering from furosemide-induced dehydration. ANIMALS: 6 horses. PROCEDURES: Voluntary WI, body weight, and blood and urine constituents were measured before and after induction of dehydration by furosemide administration and overnight withholding of water; these same variables also were measured during a 36-hour rehydration period. Each horse was evaluated 4 times with random application of 4 treatments (electrolyte pastes) that provided 0.5 g of KCl/kg of body weight, 0.5 g of NaCl/kg, 0.25 g of NaCl and 0.25 g of KCl/kg, or no electrolytes (control treatment). Electrolyte pastes were administered 3 times (4, 8, and 12 hours after start of the rehydration period). RESULTS: Administration of all electrolyte pastes resulted in significantly greater voluntarily WI, compared with the control treatment, and was accompanied by significantly greater recovery of body weight when NaCl was a component of the paste. Administration of NaCl and NaCl-KCl pastes tended to produce a state of transient hyperhydration; however, electrolyte administration also resulted in significantly greater urine production and electrolyte excretion during the final 24 hours of the rehydration period. Adverse effects of oral administration of hypertonic electrolyte pastes were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of electrolyte pastes to dehydrated horses increases voluntary WI and improves rehydration during the rehydration period. Rehydration is more rapid and complete when NaCl is a component of the electrolyte paste.     

Furosemide and sodium bicarbonate-induced alkalosis in the horse and response to oral KCl or NaCl therapy

Metabolic alkalosis was induced in 10 clinically normal horses by administration of furosemide (1 mg/kg of body weight, IM) followed 4.5 hours later by sodium bicarbonate (NaHCO3; 500 g in 8 L water) via nasogastric tube. Furosemide diuresis resulted in a mean weight loss of 21.1 kg, which was associated with small, but significant, increases in venous blood pH, bicarbonate, and plasma protein concentrations (P less than 0.001), while plasma potassium, chloride, and calcium concentrations declined significantly (P less than 0.001). Oral administration of the hypertonic NaHCO3 solution resulted in clinical evidence of hypovolemia, which was accompanied by a marked increase (P less than 0.001) in plasma protein concentration. Seven of the 10 horses developed signs of neuromuscular excitability, as evidenced by muscle fasciculations, and 5 of the horses developed diaphragmatic flutter. Hypernatremia was transiently induced, but it resolved as the horses were allowed access to water. The alkalosis induced by furosemide and NaHCO3 was profound and persisted for a 24-hour period and was associated with marked hypochloremia and hypokalemia. Partial replacement of the electrolyte deficits and correction of the metabolic alkalosis was attempted, using 1,000 mEq of NaCl or KCl given as an isotonic solution via nasogastric tube. In the KCl-treated group, there was a prompt and significant decline in venous blood pH and bicarbonate concentration (P less than 0.001) accompanied by a significant increase in plasma potassium concentration (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of trimethoprim/sulphachlorpyridazine in horses after oral, nasogastric and intravenous administration

In the present study, the pharmacokinetic parameters of a trimethoprim/sulphachlorpyridazine preparation following intravenous administration, administration by nasogastric tube and administration with concentrate were determined in the horse. Eight adult horses were dosed at 1 week intervals in a sequentially designed study at a dose of 5 mg/kg trimethoprim (IMP) and 25 mg/kg sulphachlorpyridazine (SCP) on all occasions. Plasma concentrations of both drugs were measured serially for 48 h. Pharmacokinetic parameters of clinical importance (distribution and elimination half-lives, clearance, bioavail-ability, volume of distribution) were determined both for TMP and SCP. Following intravenous administration, the volume of distribution at steady-state (V_d(33) was significantly larger for TMP (1.51 ± 0.25 L/kg than for SCP (0.26 ± 0.05 L/kg. The clearance was 7.73 ± 2.26 mL/min-kg for TMP and 2.64 ± 0.48 mL/min·kg for SCP. For both TMP and SCP, mean peak plasma concentrations (C_max) and the bioavailabilities (F) were reduced significantly when the drugs were mixed with concentrate (ct) as compared with those after nasogastric administration (ngt) (F_ct= 44.3 ± 10.7% vs. F_ngt= 68.3 ± 12.5% for TMP; F_ct= 46.3 ± 8.9% vs. F_ngt= 67.3 ±13.7% for SCP). Following the administration of TMP and SCP mixed with concentrate, the plasma concentration—time curves showed a biphasic absorption pattern in all horses. The first peak occurred 1–2 h and the second peak 8–10 h after administration of the combination preparation. Based on the pharmacokinetic data obtained and the published in vitro sensitivity data, it may be predicted that TMP and SCP given intravenously or by nasogastric tube at a dose of 5 mg/kg and 25 mg/kg respectively and a dosage interval of 8–12 h would result in sufficiently high plasma concentrations for effectiveness against susceptible bacteria. The single oral administration of TMP and SCP mixed with concentrate did not result in effective plasma concentrations. Further studies are needed to investigate whether higher plasma concentrations would be achieved by a multiple dosing scheme for several days.     

Water intake and fluid shifts in horses: effects of hydration status during two exercise tests

In the present study, the main objective was to study factors affecting postexercise voluntary water intake in horses. Four Standardbred horses (mean +/- s.e. bwt 500 +/- 8 kg) were used to study water intake and effects of altering hydration status before an incremental exercise test (INCR) and a 40 min constant velocity exercise test (CONST) on a treadmill. Exercise was performed during normohydration (N), after dehydration for 24 h (DEH) and after hyperhydration with 12 l water 30 min before exercise (HH). DEH resulted in a bodyweight loss of 3% and there were signs of some fluid uptake prior to exercise in both HH trials. By the end of the INCR, the calculated change in plasma volume (PVcalc) was -13 +/- 1, -21 +/- 1 and -11 +/- 3% in the N, DEH and HH trials, respectively. During the highest exercise velocities a hypotonic shift of fluid was seen in all INCR trials. There was a greater accumulation of plasma lactate (pLA) in HH-than in N-INCR, probably caused by the extra weight to be carried. CONST induced a similar fluid loss (3%) in all trials, but the decrease in PVcalc at the end of exercise was significantly smaller in HH (-7 +/- 2%) than in N (-14 +/- 1%) and DEH (-19 +/- 2%). In DEH-INCR and DEH-CONST, plasma sodium concentration (pNa) was higher than in N until drinking water was offered 1 h postexercise. In the presence of both an increased pNa and a decrease in PVcalc when dehydrated, the horses drank immediately when offered water postexercise. In N-CONST, there was a significant decrease in calculated PVcalc (-10 +/- 2%) but no increase in pNa when water was given and in this trial the horses rehydrated less rapidly. Plasma aldosterone concentration (PAC) had increased to the same magnitude in all trials after about 10 min, irrespective of type of exercise or hydration status. It was concluded that when both an osmotic and hypovolemic thirst stimulus was present, the horses rehydrated more rapidly postexercise.     

Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration

The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume of distribution [V(d(ss))] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (C(max)) was 3.47 mug/mL and an apparent half-life (t(1/2)) of 1.64 h. Bioavailability was approximately 5.0%. The AUC(ISF):AUC(plasma) ratio was 80.55% which corresponded to the percentage protein-unbound drug in the plasma (77.07%). The t(1/2) in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 +/- 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 microg/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram-positive bacteria (MIC < or = 0.5 microg/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.     

Influence of Medetomidine on Acid-base Balance and Urine Excretion in Goats

Raekallio M., M. Hackzell and L. Eriksson: Influence of medetomidine on acid-base balance and urine excretion in goats. Acta vet. scand. 1994,35,283-288.– Seven goats were given medetomidine 5 μg/kg as an iv bolus injection. Venous blood samples were taken repeatedly and urine was collected continuously via a catheter up to 7h after the injection.Medetomidine caused deep clinical sedation. Base excess, pH and PCO₂ in venous blood rose after medetomidine administration. There were no significant changes in plasma concentrations of sodium, calcium, magnesium, creatinine or osmolality, whereas potassium and bicarbonate concentrations increased, and phosphate and chloride decreased. Medetomidine increased plasma glucose concentration, and in 4 of 7 goats glucose could also be detected in urine. Medetomidine did not influence urine flow rate, free water clearance, bicarbonate and phosphate excretion or pH, but renal chloride, sodium, potassium, calcium, magnesium and creatinine excretion were reduced.The results suggest that the metabolic alkalosis recorded after medetomidine administration is not caused by increased renal acid excretion.     

Evaluation of the pharmacokinetics and bioavailability of intravenously and orally administered amiodarone in horses

OBJECTIVE: To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously. ANIMALS: 6 healthy adult horses. PROCEDURE: In a cross over study, clinical signs and electrocardiographic variables were monitored and plasma and urine samples were collected. A liquid chromatography-mass spectrometry method was used to determine the percentage of protein binding and to measure plasma and urine concentrations of amiodarone and the active metabolite desethylamiodarone. RESULTS: No adverse clinical signs were observed. After IV administration, median terminal elimination half-lives of amiodarone and desethylamiodarone were 51.1 and 75.3 hours, respectively. Clearance was 0.35 L/kg x h, and the apparent volume of distribution for amiodarone was 31.1 L/kg. The peak plasma desethylamiodarone concentration of 0.08 microg/mL was attained 2.7 hours after IV administration. Neither parent drug nor metabolite was detected in urine, and protein binding of amiodarone was 96%. After oral administration of amiodarone, absorption of amiodarone was slow and variable; bioavailability ranged from 6.0% to 33.7%. The peak plasma amiodarone concentration of 0.14 microg/mL was attained 7.0 hours after oral administration and the peak plasma desethylamiodarone concentration of 0.03 microg/mL was attained 8.0 hours after administration. Median elimination half-lives of amiodarone and desethylamiodarone were 24.1 and 58.6 hours, respectively. CONCLUSION AND CLINICAL RELEVANCE: Results indicate that the pharmacokinetic distribution of amiodarone is multicompartmental. This information is useful for determining treatment regimens for horses with arrythmias. Amiodarone has low bioavailability after oral administration, does not undergo renal excretion, and is highly protein-bound in horses.     

Pharmacokinetics of meloxicam in plasma and urine of horses

OBJECTIVE: To determine pharmacokinetic parameters for meloxicam, a nonsteroidal anti-inflammatory drug, in horses. ANIMALS: 8 healthy horses. PROCEDURE: In the first phase of the study, horses were administered meloxicam once in accordance with a 2 x 2 crossover design (IV or PO drug administration; horses fed or not fed). The second phase used a multiple-dose regimen (daily oral administration of meloxicam for 14 days), with meloxicam administered at the recommended dosage (0.6 mg/kg). Plasma and urine concentrations of meloxicam were measured by use of validated methods with a limit of quantification of 10 ng/mL for plasma and 20 ng/mL for urine. RESULTS: Plasma clearance was low (mean +/- SD; 34 +/- 0.5 mL/kg/h), steady-state volume of distribution was limited (0.12 +/- 0.018 L/kg), and terminal half-life was 8.54 +/- 3.02 hours. After oral administration, bioavailability was nearly total regardless of feeding status (98 +/- 12% in fed horses and 85 +/- 19% in nonfed horses). During once-daily administration for 14 days, we did not detect drug accumulation in the plasma. Meloxicam was eliminated via the urine with a urine-to-plasma concentration that ranged from 13 to 18. Concentrations were detected for a relatively short period (3 days) after administration of the final daily dose. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study support once-daily administration of meloxicam regardless of the feeding status of a horse and suggest a period of at least 3 days before urine concentrations of meloxicam reach concentrations that could be used in drug control programs.     

Evaluation of urine sucrose concentration for detection of gastric ulcers in horses

OBJECTIVE: To evaluate the use of sucrose permeability testing to detect ulcers in the gastric squamous mucosa of horses. ANIMALS: 13 adult horses ranging from 5 to 19 years of age. PROCEDURE: Following induction of gastric ulcers by intermittent feed deprivation, horses underwent sucrose permeability testing (administration of sucrose by nasogastric intubation followed by collection of urine at 2 and 4 hours after intubation) and gastric endoscopy. Squamous ulcers were assigned a severity score (range, 0 to 3) by use of an established scoring system. Horses were subsequently administered omeprazole for 21 days, and sucrose testing and endoscopy were repeated. Pair-wise comparisons of urine sucrose concentration were made between horses with induced ulcers before and after omeprazole treatment. Urine sucrose concentrations also were compared on the basis of ulcer severity score. RESULTS: Urine sucrose concentrations and ulcer severity scores were significantly higher in horses with induced ulcers before omeprazole treatment than after treatment. Urine sucrose concentrations were significantly higher for horses with ulcer severity scores > 1. Use of a cut-point value of 0.7 mg/mL revealed that the apparent sensitivity and specificity of sucrose permeability testing to detect ulcers with severity scores > 1 was 83% and 90%, respectively. Results were similar after adjusting sucrose concentrations for urine osmolality. CONCLUSIONS AND CLINICAL RELEVANCE: Urine sucrose concentration appears to be a reliable but imperfect indicator of gastric squamous ulcers in horses. Sucrose permeability testing may provide a simple, noninvasive test to detect and monitor gastric ulcers in horses.     

Use of the advanced micro-osmometer model 3300 for determination of a normal osmolality and evaluation of different formulas for calculated osmolarity and osmole gap in adult dogs

Objective: To determine a reference interval of whole blood and plasma osmolalities for dogs using the Advanced Micro Osmometer Model 3300, to compare calculated osmolarity to measured osmolality, to determine a reference osmole gap, and to determine the best formula for calculated osmolaity. Design: Prospective, observational. Setting: Tertiary referral and teaching hospital. Animals: One hundred healthy adult dogs. Interventions: None. Measurements: Serum and whole blood biochemistry and osmolality assessments. Results: The mean and median of the measured whole blood osmolality were 323 and 320 mOsm/kg, respectively, with a standard deviation of 13.2 mOsm/kg. The mean and median of the measured plasma osmolality were 313 and 310 mOsm/kg, respectively, with a standard deviation of 13.2 mOsm/kg. The formula that was closest to predicting the measured whole blood and plasma osmolality was ((1.86(Na+K))+(BUN/2.8)+(Glucose/18))/0.93 followed closely by the traditional formula of (2(Na+K))+(BUN/2.8)+(Glucose/18). The mean calculated osmolarities using these formulas were 314.1 and 313.25 mOsm/L, respectively. The mean osmole gap using these formulas was 3.49 and 4.41 mOsm, respectively, for whole blood and ?2.01 and ?1.1 mOsm, respectively, for plasma. Conclusion: The Advanced Micro Osmometer Model 3300 was successful in measuring the osmolality in relative agreement with the current published reference intervals for osmolality. Measured osmolality correlated well with traditional calculated osmolarity.     

Excess cortisol interferes with a principal mechanism of resistance to dehydration in Bos indicus steers

This study investigated the effects of excess cortisol on physiological mechanisms that resist dehydration in Bos indicus steers (n = 31, 2 yr of age, 193 +/- 21.47 kg mean BW) during a 90-h period. Steers were assigned randomly to one of four groups: 1) no water/no cortisol (n = 8), 2) water/no cortisol (n = 8), 3) no water/cortisol (n = 8), and 4) water/cortisol (n = 7). Animals allocated to cortisol treatment groups were given 0.1 mg x kg BW(-1) x h(-1) of hydrocortisone suspended in isotonic saline for the duration of the study. Total body water, osmolality, hematocrit, urine output, feed and water intake, and plasma concentrations of arginine vasopressin (AVP), angiotensin II (AII), electrolytes, total protein, and albumin were determined at 24-h intervals for 90 h. In the presence of excess plasma cortisol, total body water was maintained in the presence of a water deprivation insult for 90 h, whereas hydration indices, such as total plasma protein and albumin, did not change, supporting the body water data. However, plasma osmolality increased for the water-deprived groups from 24 h (P = 0.008). Hematocrit did not reflect dehydration in any group. Water deprivation induced an increase in endogenous plasma cortisol concentrations after 60 h of the study (P = 0.028). Plasma concentrations of AVP increased with water deprivation (P = 0.006). Excess cortisol decreased the plasma concentration of AVP at 72 h only (P = 0.027) and suppressed plasma concentrations of AII at 24 and 72 h (P < 0.001 and P = 0.036, respectively). Animals treated with excess cortisol maintained urinary output for 48 h before decreasing at 72 h (P = 0.057), although there was no effect on water or feed intake. Water deprivation increased plasma sodium concentrations (P < 0.05) until 72 h, whereas potassium decreased under the influence of excess plasma cortisol (P = 0.001) at 24 h. Water deprivation increased plasma chloride concentration at 72 and 90 h (P = 0.051 and P = 0.026, respectively). Plasma phosphorus decreased at 24 h (P = 0.001) and remained at lesser concentrations for the duration of the study (P = 0.05). These results highlight the complexity of endocrine interactions associated with water balance in Bos indicus steers. We accept our hypothesis that, in the presence of excess cortisol, the renin-angiotensin-aldosterone axis is suppressed; however, homeostasis is achieved through other physiological systems.     

Pharmacokinetics of ibuprofen after intravenous and oral administration and assessment of safety of administration to healthy foals.

OBJECTIVE: To determine pharmacokinetics of ibuprofen in healthy foals and to determine clinical effects after oral administration for 6 days. ANIMALS: 7 healthy 5- to 10-week-old foals. PROCEDURE: Serum concentrations of ibuprofen were measured after IV and oral (nasogastric tube) administration at dosages of 10 and 25 mg/kg of body weight. Foals were given ibuprofen (25 mg/kg, PO, q 8 h) as a paste for 6 days. Serum and urine were obtained before and after the 6-day period. RESULTS: Half-life of elimination (Kel t1/2) of IV-administered ibuprofen (ie, 10 and 25 mg/kg), was 79 and 108 minutes, maximal serum concentration (C(MAX)) was 82 and 160 microg/ml, and clearance was 0.003 and 0.002 L/kg/min, respectively. At the higher dosage, clearance was significantly lower and C(MAX) was significantly higher. Ibuprofen given via nasogastric tube resulted in Kel t1/2 of 81 and 100 minutes and C(MAX) of 22 and 52 microg/ml for 10 and 25 mg/kg, respectively. The absorption half-life was 13 minutes, and bioavailability ranged from 71 to 100%. Foals remained healthy during oral administration of ibuprofen. Serum urea nitrogen, creatinine, and L-iditol dehydrogenase values increased significantly, and gamma-glutamyltransferase (GGT) activity and osmolality decreased, but all measurements remained within reference ranges. Urine GGT activity doubled. Necropsy did not reveal gross or histologic renal lesions attributable to ibuprofen. Acute gastric ulcers were evident in 1 foal, although clinical signs of ulcers were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: Ibuprofen can be given safely to healthy foals at dosages < or = 25 mg/kg every 8 hours for up to 6 days.     

Plasma and urine nitric oxide concentrations in horses given below a low dose of endotoxin.

OBJECTIVE: To quantify plasma and urine nitric oxide (NO) concentrations before and after low-dose endotoxin infusion in horses. ANIMALS: 11 healthy adult female horses. Procedure-Eight horses were given endotoxin (35 ng/kg of body weight,i.v.) over 30 minutes. Three sentinel horses received an equivalent volume of saline (0.9% NaCl) solution over the same time. Clinical signs of disease and hemodynamic variables were recorded, and urine and plasma samples were obtained to measure NO concentrations prior to endotoxin infusion (t = 0) and every hour until postinfusion hour (PIH) 6, then every 2 hours until PIH 24. Blood for hematologic and metabolic analyses and for serum cytokine bioassays were collected at 0 hour, every hour until PIH 6, every 2 hours through PIH 12, and finally, every 6 hours until PIH 24. RESULTS: Differences in plasma NO concentrations across time were not apparent, but urine NO concentrations significantly decreased at 4 and 20 to 24 hours in endotoxin-treated horses. Also in endotoxin-treated horses, alterations in clinical signs of disease, and hemodynamic, metabolic, and hematologic variables were significant and characteristic of endotoxemia. Serum interleukin-6 (IL-6) activity and tumor necrosis factor (TNF) concentrations were increased above baseline values from 1 to 8 hours and 1 to 2 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma and urine NO concentrations did not increase in horses after administration of a low dose of endotoxin, despite induction of an inflammatory response, which was confirmed by increased TNF and IL-6 values characteristic alterations in clinical signs of disease, and hematologic, hemodynamic and metabolic variables.     

Effects of oral administration of a commercial activated charcoal suspension on serum osmolality and lactate concentration in the dog

The purpose of this investigation was to determine the effects of an activated charcoal (AC) suspension containing propylene glycol and glycerol on serum osmolality, osmolal gap, and lactate concentration in dogs. Six healthy adult dogs were administered 4 g/kg AC in a commercially available suspension that contained propylene glycol and glycerol as vehicles. Blood samples were taken before and 1, 4, 6, 8, 12, and 24 hours after the administration of the test suspension. Samples were analyzed for osmolality, blood gases, and concentrations of lactate, sodium, potassium, serum urea nitrogen, and glucose. Osmolal gaps were calculated for each time point. Mean serum osmolality, osmolal gap, and lactate concentration were significantly increased after suspension administration compared to baseline. Serum osmolality increased from 311 mOsm/kg at baseline to 353 mOsm/kg, osmolal gap increased from 5 to 52 mOsm/kg, and lactate concentration increased from 1.9 to 4.5 mmol/L after suspension administration (all P < .01). Three of the 6 dogs vomited between 1 and 3 hours after the administration of the test suspension, and 4 of 6 dogs were lethargic. All dogs drank frequently after AC administration. Commercial AC suspension administered at a clinically relevant dose increases serum osmolality, osmolal gap, and lactate concentration in dogs. These laboratory measures and the clinical signs of vomiting, lethargy, and increased frequency of drinking might complicate the diagnosis or monitoring of some intoxications (such as ethylene glycol) in dogs that have previously received AC suspension containing propylene glycol, glycerol, or both as vehicles.     

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.