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- Author or Editor: Mark V. Crisman x
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Abstract
Objective
To determine pharmacokinetic variables that describe disposition of ketoprofen after its IV administration to foals < 24 hours old.
Animals
6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration.
Procedure
Ketoprofen was administered IV to foals at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma samples was analyzed, using high-performance liquid chromatography. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined times during a 48-hour period. Samples were centrifuged, and plasma was frozen at −70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by use of Akaike's information criterion analysis.
Results
Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance (normalized for body weight) was significantly lower than that determined for adult horses. Volume of distribution (normalized for body weight) was larger than that determined for adult horses. Mean (harmonic) plasma half-life for healthy foals < 24 hours old was 4.3 hours.
Clinical Relevance
Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals < 24 hours old should be different from the dose administered to adult horses. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to produce comparable therapeutic concentrations; longer dose intervals, based on clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1998;59:290–292)
Summary
Single doses (2.2 mg/kg of body weight) of phenylbutazone (pbz) were administered iv to 6 neonatal horses (5 to 17 hours old at time of dosing). Plasma concentrations of pbz and its metabolite oxyphenbutazone were monitored serially for 120 hours after drug administration. Pharmacokinetic variables were calculated, using 1- and 2-compartment open models. Descriptive equations from the best model for each foal were then used to derive model-independent variables describing pbz disposition. Median volume of distribution at steady-state was 0.274 L/ kg (range, 0.190 to 0.401 L/kg). Median terminal half-life was 7.4 (6.4 to 22.1) hours, and median total plasma clearance of pbz for foals in this study was 0.018 L/kg/h (range, 0.013 to 0.038 L/kg/h). Volume of distribution was larger, half-life was longer, and total clearance was lower, compared with similar values reported for administration of pbz to adult horses.
SUMMARY
Bovine whey samples were evaluated by use of lymphocyte-transformation tests to determine their effect on lymphocyte blastogenesis. Whey samples from mammary glands with clinical mastitis strongly inhibited dna synthesis and blastogenesis in lymphocytes stimulated with mitogens or dividing because of bovine leukemia virus infection. Whey samples from apparently healthy glands either did not inhibit lymphocyte dna synthesis or inhibited it to a lesser degree than did whey from mastitic glands. Degree of inhibition was dose-dependent. The molecules causing inhibition were noncytotoxic and underwent minimal binding to the lymphocytes. Inhibitory molecules were susceptible to various proteolytic and glycolytic enzymes, indicating a glycoprotein-like structure. Whey inhibited incorporation of thymidine if it was in the cell cultures during the early stages of stimulation. Incubation of lymphocytes in whey that inhibited thymidine incorporation did not affect dna synthesis in subsequent culturing of the same cells without whey. Degree of inhibition was affected by the method of whey preparation.
Abstract
Objective
To determine pharmacokinetic variables that describe the disposition of flunixin after IV administration of flunixin meglumine to foals < 24 hours old.
Animals
6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours).
Procedure
Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined intervals over a 48-hour period. Samples were centrifuged, and plasma was frozen at −70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by Akaike's information criterion analysis.
Results
Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance was significantly lower than that determined for older foals and adult horses. Volume of distribution was larger than that determined for adults. Mean plasma halflife for healthy foals < 24 hours old was 8.5 hours.
Conclusions and Clinical Relevance
Although additional factors (eg, dehydration or sepsis) must be considered on a case-by-case basis, flunixin meglumine should be administered differently to foals < 24 hours old, compared with adults. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to induce comparable therapeutic concentrations; longer dose intervals, on the basis of clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1996;57:1759–1761)
Abstract
Objective—To determine concentrations of IgA and IgG subclasses in serum, colostrum, milk, and nasal wash samples of adult horses and foals.
Animals—Seven 2-year-old Welsh ponies, 27 adult mixed-breed horses, and 5 Quarter Horse mares and their foals.
Procedure—Serum was obtained from ponies and adult horses. Colostrum and milk were obtained from mares and serum and nasal wash samples from their foals immediately after parturition and on days 1, 7, 14, 28, 42, and 63. Nasal wash samples were also obtained from 23 adult horses. Concentrations of immunoglobulins were determined by use of inhibition ELISA. To determine transfer of maternal isotypes to foals, concentrations in colostrum and milk were compared with those in foal serum. Serum half-lives of isotypes in foals were also determined.
Results—IgGb was the most abundant isotype in serum and colostrum from adult horses, whereas IgA was the predominant isotype in milk. The major isotype in nasal secretions of adult horses and foals ≥ 28 days old was IgA, but IgGa and IgGb were the major isotypes in nasal secretions of foals ≤ 14 days old. Serum half lives of IgGa, IgGb, IgG(T), and IgA in foals were 17.6, 32, 21, and 3.4 days, respectively.
Conclusions and Clinical Relevance—The early immunoglobulin repertoire of neonatal foals comprised IgGa, IgG(T), and IgA; endogenous synthesis of IgGb could not be detected until 63 days after birth. The restricted repertoire of immunoglobulins in foals may influence humoral immune responses to vaccination. (Am J Vet Res 2000;61:1099–1105)
Abstract
Objective—To measure the ascorbic acid (AA) concentration in bronchoalveolar lavage fluid (BALF) and cellular glutathione peroxidase (cGPx) activity in RBCs and WBCs from peripherally obtained blood and in cells from BALF to determine whether differences existed between the 2 major redox systems in recurrent airway obstruction (RAO)-affected and -nonaffected (control) horses and between systemic and local pulmonary responses in the glutathione redox system.
Animals—16 adult horses in pairs: 8 healthy (control) and 8 RAO-affected horses.
Procedures—Physical examination data and biological samples were collected from horses before (remission), during, and after (recovery) environmental challenge with dusty straw and hay. At each stage, BALF cell AA concentration and RBC, WBC, and BALF cell cGPx activity were measured.
Results—Compared with control horses, RAO-affected horses had significantly higher cGPx activity in RBCs at all points and in WBCs during remission and challenge. The BALF cell cGPx activity was higher in RAO-affected horses during recovery than during remission The BALF cell AA concentration did not differ significantly in control horses at any point, but total and free AA concentrations were significantly lower in RAO-affected horses during the challenge period than during remission and recovery periods.
Conclusions and Clinical Relevance—High cGPx activity suggested this redox system was upregulated during exposure to dusty straw and hay to combat oxidative stress, as AA was depleted in RAO-affected horses. The relative delay and lack of comparative increase in cGPx activity within the local environment (represented by BALF cells), compared with that in RBCs and WBCs, might contribute to disease in RAO-affected horses.
Abstract
Objective—To determine whether a limited sampling time method based on serum iohexol clearance (Cliohexol) would yield estimates of glomerular filtration rate (GFR) in clinically normal horses similar to those for plasma creatinine clearance (Clcreatinine).
Animals—10 clinically normal adult horses.
Procedures—A bolus of iohexol (150 mg/kg) was administered IV, and serum samples were obtained 5, 20, 40, 60, 120, 240, and 360 minutes after injection. Urinary clearance of exogenous creatinine was measured during three 20-minute periods. The GFR determined by use of serum Cliohexol and plasma Clcreatinine was compared with limits of agreement plots.
Results—Values obtained for plasma Clcreatinine ranged from 1.68 to 2.69 mL/min/kg (mean, 2.11 mL/min/kg). Mean serum Cliohexol was 2.38 mL/min/kg (range, 1.95 to 3.33 mL/min/kg). Limits of agreement plots indicated good agreement between the methods.
Conclusions and Clinical Relevance—Use of serum Cliohexol yielded estimates of GFR in clinically normal adult horses similar to those for plasma Clcreatinine. This study was the first step in the evaluation of the use of serum Cliohexol for estimating GFR in adult horses.
Abstract
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. ( Am J Vet Res 2004;65:687–694)
Abstract
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. (Am J Vet Res 2004;65:695–704)
Abstract
Objective—To evaluate healing of pinch-grafted wounds on the distal aspect of the limbs of ponies bandaged with equine amnion or a standard nonadherent wound dressing material.
Animals—6 ponies.
Procedure—A 2.5 × 2.5-cm full-thickness section of skin was removed from the dorsal aspect of each limb at the midpoint of the metacarpus or metatarsus. Six days later, wounds were grafted with partial-thickness pinch grafts. Half the wounds were bandaged with amnion, and the other half were bandaged with a nonadherent dressing. Bandages were changed every 3 days until wound healing was complete. At each bandage change, numbers of grafts lost were recorded, and wounds were measured.
Results—Percentage of grafts lost from wounds bandaged with amnion was not significantly different from percentage lost from wounds bandaged with the nonadherent dressing. Median healing time for wounds bandaged with amnion (30 days) was significantly less than median healing time for wounds bandaged with the nonadherent dressing (39 days). All wounds were healed by day 45.
Conclusions and Clinical Relevance—Results suggest that amnion can be used for bandaging pinchgrafted wounds on the distal aspect of the limbs of ponies. (Am J Vet Res 2000;61:326–329)
