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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)

Free access
in American Journal of Veterinary Research

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)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To compare systemic bioavailability and duration for therapeutic plasma concentrations and cardiovascular, respiratory, and analgesic effects of morphine administered per rectum, compared with IV and IM administration in dogs.

Animals—6 healthy Beagles.

Procedure—In a randomized study, each dog received the following: morphine IV (0.5 mg/kg of body weight), morphine per rectum (1, 2, and 5 mg/kg as a suppository and 2 mg/kg as a solution), and a control treatment. Intramuscular administration of morphine (1 mg/kg) was evaluated separately. Heart and respiratory rates, systolic, diastolic, and mean blood pressures, adverse effects, and plasma morphine concentrations were measured. Analgesia was defined as an increase in response threshold, compared with baseline values, to applications of noxious mechanical (pressure) and thermal (heat) stimuli. Data were evaluated, using Friedman repeated-measures ANOVA on ranks and Student-Newman-Keuls post-hoc t-tests.

Results—Significant differences were not found in cardiovascular, respiratory, or analgesia values between control and morphine groups. Overall systemic bioavailability of morphine administered per rectum was 19.6%. Plasma morphine concentration after administration of the highest dose (5 mg/kg) as a suppository was significantly higher than concentrations 60 and 360 minutes after IV and IM administration, respectively. A single route of administration did not consistently fulfill our criteria for providing analgesia.

Conclusions and Clinical Relevance—Rectal administration of morphine did not increase bioavailability above that reported for oral administration of morphine in dogs. Low bioavailability and plasma concentrations limit the clinical usefulness of morphine administered per rectum in dogs. (Am J Vet Res 2000;61:24–28)

Full access
in American Journal of Veterinary Research

SUMMARY

Objective

To identify the effect of Pasteurella haemolytica lipopolysaccharide (LPS) and leukotoxin (LKT) on spontaneous and calcium ionophore-induced histamine and inflammatory mediator release from isolated bovine lung parenchyma.

Sample Population

Lungs from 8 healthy cattle.

Procedure

Isolated bovine lung parenchyma was incubated in vitro for 2 hours with LKT or LPS, and spontaneous and induced release of inflammatory mediators was determined.

Results

LKT and LPS increased spontaneous release of histamine and leukotriene B4. In addition, incubation with LPS increased spontaneous release of prostaglandin E2. Moreover, a differential effect of the 2 toxins on calcium ionophore-induced inflammatory mediator release was observed. LKT specifically primed isolated lung parenchyma to release leukotriene B4 and thromboxane B2 in response to calcium ionophore, whereas LPS did not alter the profile of prostanoids released by bovine lung tissue exposed to calcium ionophore.

Conclusions

Pasteurella haemolytica toxins have a direct effect on bovine lung parenchyma, causing release of inflammatory mediators, which contribute to response to infection. Furthermore, bacterial toxins (LKT in this study) may sensitize tissues to the effects of other irritant stimuli, amplifying the inflammatory response. (Am J Vet Res 1997;58:1227–1231)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate calcium balance and parathyroid gland function in healthy horses and horses with enterocolitis and compare results of an immunochemiluminometric assay (ICMA) with those of an immunoradiometric assay (IRMA) for determination of serum intact parathyroid hormone (PTH) concentrations in horses.

Animals—64 horses with enterocolitis and 62 healthy horses.

Procedures—Blood and urine samples were collected for determination of serum total calcium, ionized calcium (Ca2+) and magnesium (Mg2+), phosphorus, BUN, total protein, creatinine, albumin, and PTH concentrations, venous blood gases, and fractional urinary clearance of calcium (FCa) and phosphorus (FP). Serum concentrations of PTH were measured in 40 horses by use of both the IRMA and ICMA.

Results—Most (48/64; 75%) horses with enterocolitis had decreased serum total calcium, Ca2+, and Mg2+ concentrations and increased phosphorus concentrations, compared with healthy horses. Serum PTH concentration was increased in most (36/51; 70.6%) horses with hypocalcemia. In addition, FCa was significantly decreased and FP significantly increased in horses with enterocolitis, compared with healthy horses. Results of ICMA were in agreement with results of IRMA.

Conclusions and Clinical Relevance—Enterocolitis in horses is often associated with hypocalcemia; 79.7% of affected horses had ionized hypocalcemia. Because FCa was low, it is unlikely that renal calcium loss was the cause of hypocalcemia. Serum PTH concentrations varied in horses with enterocolitis and concomitant hypocalcemia. However, we believe low PTH concentration in some hypocalcemic horses may be the result of impaired parathyroid gland function. ( Am J Vet Res 2001;62:938–947)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of IV administration of enalaprilat on cardiorespiratory and hematologic variables as well as inhibition of angiotensin converting enzyme (ACE) activity in exercising horses.

Animals—6 adult horses.

Procedure—Horses were trained by running on a treadmill for 5 weeks. Training was continued throughout the study period, and each horse also ran 2 simulated races at 120% of maximum oxygen consumption. Three horses were randomly selected to receive treatment 1 (saline [0.9% NaCl] solution), and the remaining 3 horses received treatment 2 (enalaprilat; 0.5 mg/kg of body weight, IV) before each simulated race. Treatment groups were reversed for the second simulated race. Cardiorespiratory and hematologic data were obtained before, during, and throughout the 1-hour period after each simulated race. Inhibition of ACE activity was determined during and after each race in each horse.

Results—Exercise resulted in significant increases in all hemodynamic variables and respiratory rate. The pH and PO2 of arterial blood decreased during simulated races, whereas PCO2 remained unchanged. Systemic and pulmonary blood pressure measurements and arterial pH, PO2, and PCO2 returned to baseline values by 60 minutes after simulated races. Enalaprilat inhibited ACE activity to < 25% of baseline activity without changing cardiorespiratory or blood gas values, compared with horses administered saline solution.

Conclusions and Clinical Relevance—Enalaprilat administration almost completely inhibited ACE activity in horses without changing the hemodynamic responses to intense exercise and is unlikely to be of value in preventing exercise-induced pulmonary hemorrhage. (Am J Vet Res 2001;62:1008–1013)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the anesthetic, cardiorespiratory, and metabolic effects of 4 IV anesthetic regimens in Thoroughbred horses recuperating from a brief period of maximal exercise.

Animals—6 adult Thoroughbreds.

Procedure—Horses were preconditioned by exercising them on a treadmill. Each horse ran 4 simulated races, with a minimum of 14 days between races. Races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until fatigued or for a maximum of 2 minutes. Two minutes after exercise, horses received a combination of xylazine hydrochloride (2.2 mg/kg of body weight) and acepromazine maleate (0.04 mg/kg) IV. Five minutes after exercise, horses received 1 of the following 4 IV anesthetic regimens: ketamine hydrochloride (2.2 mg/kg); ketamine (2.2 mg/kg) and diazepam (0.1 mg/kg); tiletamine hydrochloride-zolazepam hydrochloride (1 mg/kg); and guaifenesin (50 mg/kg) and thiopental sodium (5 mg/kg). Treatments were randomized. Cardiopulmonary indices were measured, and samples of blood were collected before and at specific times for 90 minutes after each race.

Results—Each regimen induced lateral recumbency. The quality of induction and anesthesia after ketamine administration was significantly worse than after other regimens, and the duration of anesthesia was significantly shorter. Time to lateral recumbency was significantly longer after ketamine or guaifenesinthiopental administration than after ketaminediazepam or tiletamine-zolazepam administration. Arterial blood pressures after guaifenesin-thiopental administration were significantly lower than after the other regimens.

Conclusions and Clinical Relevance—Anesthesia can be safely induced in sedated horses immediately after maximal exercise. Ketamine-diazepam and tiletamine- zolazepam induced good quality anesthesia with acceptable perturbations in cardiopulmonary and metabolic indices. Ketamine alone and guaifenesinthiopental regimens are not recommended. (Am J Vet Res 2000;61:1545–1552)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetic disposition of IV administered caffeine in healthy Lama spp camelids.

Animals—4 adult male alpacas and 4 adult female llamas.

Procedures—Caffeine (3 mg/kg) was administered as an IV bolus. Plasma caffeine concentrations were determined by use of high-performance liquid chromatography in 6 animals and by use of liquid chromatography-mass spectrometry in 2 llamas.

Results—Median elimination half-life was 11 hours (range, 9.3 to 29.8 hours) in alpacas and 16 hours (range, 5.4 to 17 hours) in llamas. The volume of distribution at steady state was 0.60 L/kg (range, 0.45 to 0.93 L/kg) in alpacas and 0.75 L/kg (range, 0.68 to 1.15 L/kg) in llamas. Total plasma clearance was 44 mL/h/kg (range, 24 to 56 mL/h/kg) in alpacas and 42 mL/h/kg (range, 30 to 109 mL/h/kg) in llamas.

Conclusions and Clinical Relevance—High-performance liquid chromatography and liquid chromatography-mass spectrometry were suitable methods for determination of plasma caffeine concentrations in alpacas and llamas. Plasma caffeine concentration-time curves were best described by a 2-compartment model. Elimination half-lives, plasma clearance, volume of distribution at steady state, and mean residence time were not significantly different between alpacas and llamas. Intravenous administration of caffeine at a dose of 3 mg/kg did not induce clinical signs of excitement.

Full access
in American Journal of Veterinary Research

Summary

In August 1986, an extensive serosurvey for prevalence of IgG and IgM antibodies against Ehrlichia risticii, the causative agent of equine monocytic ehrlichiosis (eme), was performed at 2 Ohio racetracks, River Downs (rd) and Beulah Park (bp). Of 840 horses at rd and 574 at bp, 13 and 20%, respectively, were IgG antibody-positive (by indirect fluorescent antibody test results), with antibody titer ranging from 1:20 to 1:10,240. The titer observed at highest frequency at both racetracks was 1:80. A higher proportion of horses was ill at rd (operating during the summer months) than at bp (winter track). Of ill horses, 41% (24/58) at rd and 58% (11/19) at bp were seropositive. At rd, 70% (589/840) of all horses and 95% (102/107) of IgG seropositive horses had been stabled only at rd during the month prior to testing.

Analysis of these sera by use of an elisa to detect IgM antibody against E risticii antigen indicated that at rd, 42% (57/137) of the seropositive horses were IgM seropositive. At bp, 17% (20/120) of seropositive horses were IgM seropositive. The larger number of IgM seropositive horses at rd indicates that more horses were recently infected at rd than at bp (P = 0.0001). Therefore, at least half the seropositive horses at rd seemed to have acquired the infection at rd. These serosurvey data also indicate that at bp and rd, 78% (85/109) and 91% (111/122) of IgG seropositive horses, respectively, had subclinical infection. At ≤ 1:40 titer, there was no difference in seropositive rates between healthy and ill horses. However, the higher the titer, the greater the difference in seropositive rates between healthy and ill horses. Thus, the higher the titer, the more reliable the serodiagnosis of eme seems to be. In contrast, sera submitted from 285 horses in Ohio for serologic testing for E risticii had a higher (63%) positivity rate than sera from horses of the racetrack serosurvey. Of 120 horses with clinical signs compatible with eme, 69% were seropositive. Typical clinical signs of eme in seropositive horses were those of enteric disease (72%; 60/83), with laminitis being a secondary sign (12%; 10/83). Results indicate that seroprevalence is much greater than prevalence of clinical disease. Combination of IgG and IgM testing with horse movement history should help to identify the location of actual infection.

Free access
in Journal of the American Veterinary Medical Association

SUMMARY

Pharmacokinetics and bioavailability of rifampin in adult sheep were investigated by use of high-performance liquid chromatography for determination of serum concentrations. Eight adult ewes were given rifampin po at the rate of 50 mg of rifampin/kg of body weight. Three weeks after the first experiment, the sheep were given rifampin po and iv at the rate of 20 mg/kg in a cross-over design, with 1 week between treatments. Serum obtained over a 36-hour period was analyzed for rifampin and a potential metabolite, 25-desacetyl-rifampin, using reverse-phase chromatography with uv detection at 254 nm. Data were analyzed by compartmental and noncompartmental models. Analysis by the noncompartmental model of rifampin serum concentrations after iv administration yielded a mean ± sd total body clearance of 1.16 ± 0.21 ml/min/kg, apparent volume of distribution at steady state of 0.45 ± 0.06 L/kg, and terminal elimination rate constant of 0.15 ± 0.04 hour−1. The harmonic mean of the elimination half-life was 4.56 hours. Because of incomplete and continuing absorption, bioavailability was extremely variable after oral administration. Desacetylrifampin was not detected. On the basis of pharmacokinetic values, serum concentrations measured in this study, and published minimal inhibitory concentrations, the dosage of 20 mg of rifampin/kg, po, every 24 hours should provide adequate serum concentrations for treatment of rifampin-susceptible bacterial infections in sheep.

Free access
in American Journal of Veterinary Research