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Abstract

Objective—To determine the effect of administration of commercially available sodium bicarbonate (NaHCO3) on carbon 13 (13C) isotopic enrichment of carbon dioxide (CO2) in serum of horses.

Animals—7 healthy Thoroughbreds.

Procedure—Sodium bicarbonate (450 g) was administered via nasogastric intubation to horses. Horses had been fed a diet obtained from the same source and had access to water from the same source for 3 months before the study. Blood samples were collected immediately before and at 2, 4, 6, and 24 hours after administration of NaHCO3. The concentration of total CO2 in serum was measured by use of a commercial analyzer. The 13C enrichment of bicarbonate in serum was estimated by measurement of 13C enrichment of CO2 released by acidification of the serum. The 13C enrichment of commercially available NaHCO3 was also determined and compared with that of CO2 in serum of horses before administration of NaHCO3.

Results—Commercially available NaHCO3 had a 13C enrichment significantly different from that of carbon dioxide in serum of horses before treatment. Administration of NaHCO3 increased the concentration of total CO2 from pretreatment values. The 13C enrichment of CO2 in serum was only transiently and minimally affected after administration of NaHCO3.

Conclusions and Clinical Relevance—Administration of NaHCO3 was not detected by measuring 13C enrichment of CO2 in serum of horses. ( Am J Vet Res 2004;65:307–310)

Full access
in American Journal of Veterinary Research

SUMMARY

Eight adult horses were used in a study to determine ketamine's ability to reduce halothane requirement. To obtain steady-state plasma concentrations of 0.5, 1.0, 2.0, 4.0, and 8.0 μg/ml, loading doses and constant infusions for ketamine were calculated for each horse on the basis of data from other studies in which the pharmacokinetic properties of ketamine were investigated. Blood samples for determination of plasma ketamine concentrations were collected periodically during each experiment. Plasma ketamine concentrations were determined by capillary gas chromatography/mass spectrometry under electron-impact ionization conditions, using lidocaine as the internal standard. Halothane minimal alveolar concentration (mac; concentration at which half the horses moved in response to an electrical stimulus) and plasma ketamine concentration were determined after steady-state concentrations of each ketamine infusion had been reached. Plasma ketamine concentrations > 1.0 μg/ml decreased halothane mac. The degree of mac reduction was correlated directly with the square root of the plasma ketamine concentration, reaching a maximum of 37% reduction at a plasma ketamine concentration of 10.8 ± 2.7 μg/ml. Heart rate, mean arterial blood pressure, and the rate of increase of right ventricular pressure did not change with increasing plasma ketamine concentration and halothane mac reduction. Cardiac output increased significantly during ketamine infusions and halothane mac reduction. Our findings suggest that plasma ketamine concentrations > 1.0 μm/ml reduce halothane mac and produce beneficial hemodynamic effects.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To compare the cardiorespiratory, gastrointestinal, analgesic, and behavioral effects between IV and IM administration of morphine in conscious horses with no signs of pain.

Animals—6 healthy adult horses.

Procedures—Horses received saline (0.9% NaCl) solution (IM or IV) or morphine sulfate (0.05 and 0.1 mg/kg, IM or IV) in a randomized, masked crossover study design. The following variables were measured before and for 360 minutes after drug administration: heart and respiratory rates; systolic, diastolic, and mean arterial blood pressures; rectal temperature; arterial pH and blood gas variables; intestinal motility; and response to thermal and electrical noxious stimuli. Adverse effects and horse behavior were also recorded. Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were measured via liquid chromatography–mass spectrometry.

Results—No significant differences in any variable were evident after saline solution administration. Intravenous and IM administration of morphine resulted in minimal and short-term cardiorespiratory, intestinal motility, and behavioral changes. A decrease in gastrointestinal motility was detected 1 to 2 hours after IM administration of morphine at doses of 0.05 and 0.1 mg/kg and after IV administration of morphine at a dose of 0.1 mg/kg. Morphine administration yielded no change in any horse's response to noxious stimuli. Both morphine-3-glucuronide and morphine-6-glucuronide were detected in plasma after IV and IM administration of morphine.

Conclusions and Clinical Relevance—Clinically relevant doses of morphine sulfate yielded minimal and short-term behavioral and intestinal motility effects in healthy horses with no signs of pain. Neither dose of morphine affected their response to a noxious stimulus.

Full access
in American Journal of Veterinary Research

Summary

Age and species reportedly affect the pharmacokinetic variables of nonsteroidal anti-inflammatory drugs. We determined the effect of age on flunixin pharmacokinetic variables in foals during the first month of life. We also estimated the physiologic activity of the drug in neonatal foals by determining the effect of flunixin on thromboxane production during clotting of blood taken from the foals. Flunixin disposition and clearance were determined after iv administration of 1.1 mg of drug/kg of body weight to 5 healthy foals when they were 24 to 28 hours, 10 to 11 days, and 27 to 28 days old. The area under the curve (2,471 μg·min/ml), mean residence time (477 minutes), and zero-time intercept of the elimination phase (4,853 ng/ml) were significantly (P = 0.05) greater, the elimination half-life (339 minutes) and slope of the elimination phase (0.002 L/min) were significantly (P = 0.05) longer, and total body clearance (0.482 ml/min/kg) and zero-time intercept for the distribution phase (2,092 ng/ml) were significantly (P = 0.05) lower at 24 to 28 hours. At each age, a biexponential equation was best fitted to the plasma flunixin concentration from each foal. Thromboxane B2 production during clotting of blood was significantly (P = 0.05) suppressed for 12 hours after flunixin meglumine administration at all ages. Therefore, it appears that although age does alter the disposition and elimination of flunixin in neonatal foals, this effect may be of little consequence because the drug's physiologic activity in foals appears similar to that in mature horses.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of dexmedetomidine, morphine-lidocaine-ketamine (MLK), and dexmedetomidine-morphine-lidocaine-ketamine (DMLK) constant rate infusions on the minimum alveolar concentration (MAC) of isoflurane and bispectral index (BIS) in dogs.

Animals—6 healthy adult dogs.

Procedures—Each dog was anesthetized 4 times with a 7-day washout period between anesthetic episodes. During the first anesthetic episode, the MAC of isoflurane (baseline) was established. During the 3 subsequent anesthetic episodes, the MAC of isoflurane was determined following constant rate infusion of dexmedetomidine (0.5 μg/kg/h), MLK (morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine, 0.6 mg/kg/h), or DMLK (dexmedetomidine, 0.5 μg/kg/h; morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine 0.6 mg/kg/h). Among treatments, MAC of isoflurane was compared by means of a Friedman test with Conover posttest comparisons, and heart rate, direct arterial pressures, cardiac output, body temperature, inspired and expired gas concentrations, arterial blood gas values, and BIS were compared with repeated-measures ANOVA and a Dunn test for multiple comparisons.

Results—Infusion of dexmedetomidine, MLK, and DMLK decreased the MAC of isoflurane from baseline by 30%, 55%, and 90%, respectively. Mean heart rates during dexmedetomidine and DMLK treatments was lower than that during MLK treatment. Compared with baseline values, mean heart rate decreased for all treatments, arterial pressure increased for the DMLK treatment, cardiac output decreased for the dexmedetomidine treatment, and BIS increased for the MLK and DMLK treatments. Time to extubation and sternal recumbency did not differ among treatments.

Conclusions and Clinical Relevance—Infusion of dexmedetomidine, MLK, or DMLK reduced the MAC of isoflurane in dogs. (Am J Vet Res 2013;74:963–970)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To quantitate the dose and time-related effects of morphine sulfate on the anesthetic sparing effect of xylazine hydrochloride in halothane-anesthetized horses and determine the associated plasma xylazine and morphine concentration-time profiles.

Animals—6 healthy adult horses.

Procedure—Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of halothane in O2 and characterize the anesthetic sparing effect (ie, decrease in MAC of halothane) by xylazine (0.5 mg/kg, IV) administration followed immediately by IV administration of saline (0.9% NaCl) solution, low-dose morphine (0.1 mg/kg), or high-dose morphine (0.2 mg/kg). Selected parameters of cardiopulmonary function were also determined over time to verify consistency of conditions.

Results—Mean (± SEM) MAC of halothane was 1.05 ± 0.02% and was decreased by 20.1 ± 6.6% at 49 ± 2 minutes following xylazine administration. The amount of MAC reduction in response to xylazine was time dependent. Addition of morphine to xylazine administration did not contribute further to the xylazine-induced decrease in MAC (reductions of 21.9 ± 1.2 and 20.7 ± 1.5% at 43 ± 4 and 40 ± 4 minutes following xylazine-morphine treatments for low-and high-dose morphine, respectively). Overall, cardiovascular and respiratory values varied little among treatments. Kinetic parameters describing plasma concentration-time curves for xylazine were not altered by the concurrent administration of morphine.

Conclusions and Clinical Relevance—Administration of xylazine decreases the anesthetic requirement for halothane in horses. Concurrent morphine administration to anesthetized horses does not alter the anesthetic sparing effect of xylazine or its plasma concentration-time profile. (Am J Vet Res 2004; 65:519–526)

Full access
in American Journal of Veterinary Research

Summary

Flunixin meglumine and phenylbutazone are nonsteroidal anti-inflammatory drugs commonly used for the management of colic, endotoxemia, and musculoskeletal disorders in equids. Although it is not usually recommended, there appears to be an increasing trend to use nonsteroidal anti-inflammatory drugs in combination to enhance or prolong their effects. Therefore, we studied the effect of concurrent administration of flunixin (1.1 mg/kg of body weight, iv) as flunixin meglumine and phenylbutazone (2.2 mg/kg, iv) on the pharmacokinetics of each drug and on in vitro thromboxane B2 production.

Pharmacokinetic variables calculated for each drug when given alone and in combination were similar to those reported. Serum thromboxane B2 production was significantly (P = 0.05) suppressed for 12, 8, and 24 hours after administration of flunixin, phenylbutazone, and the drugs in combination, respectively. These results indicate that although concurrent administration of these drugs at the aforementioned dosages does not alter either drug disposition or clearance, it prolongs their pharmacologic effect.

Free access
in American Journal of Veterinary Research

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.

Free access
in American Journal of Veterinary Research

Summary

Age, species, and disease state may substantially alter the disposition and clearance of pharmacologic agents. This is particularly important when drugs with low therapeutic index are used in ill neonates. Pharmacokinetic variables for phenylbutazone were determined in 24- to 32-hour-old healthy and endotoxemic calves after iv administration of a single dose (5 mg/kg of body weight, iv). Elimination halflife was 207 and 168 hours, and clearance was 0.708 and 0.828 ml/kg/h in healthy and endotoxemic calves, respectively. Intravenous infusion of endotoxin at the dose (2 μg/kg over 4 hours) given did not significantly alter any of the calculated pharmacokinetic variables. Serum thromboxane B2 concentration was significantly (P = 0.05) suppressed for 3 hours after phenylbutazone administration in healthy calves and for 4 hours in endotoxin-challenged calves. Daily administration of phenylbutazone (10 mg/kg loading, then 5 mg/kg for 9 days) to healthy and endotoxemic calves failed to induce any lesions consistent with nonsteroidal anti-inflammatory drug toxicosis.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To examine the pharmacokinetic profile of propranolol in cats before and during experimentally induced hyperthyroidism.

Animals

8 conditioned, random-source, young adult, female cats.

Procedure

Propranolol was administered IV as a single bolus and 72 hours later by mouth. Thereafter, the cats were dosed for 5 weeks with L-thyroxine (50 μg/kg of body weight, SC, once daily) to induce hyperthyroidism (serum thyroxine concentration, 217 ± 17 nmol/L). Blood samples were obtained at appropriate intervals before and during hyperthyroidism and were analyzed for plasma propranolol concentration by use of high-performance liquid chromatography.

Results

In all cats, a two-compartment model best described the control and hyperthyroid intravenous data. The change in thyroid status from euthyroid to hyperthyroid caused a significant (P < 0.05), but small reduction in propranolol area under the curve (19,932 ± 7,900 min·μg/L vs 15,911 ± 1,400 min · μg/L) after IV administration. In contrast, after oral administration during the hyperthyroid state, a twofold increase (P < 0.05) in propranolol area under the curve (105,430 ± 57,600 min·μg/L vs 226,811 ± 112,000 min·μg/L) and peak serum propranolol concentration (651 ± 247 μg/L vs 1191 ± 590 μg/L) were attributed to significant (P < 0.05) increase in propranolol bioavailability caused by increased fractional absorption (57 ± 28% vs 137 ± 73%) and decreased total body clearance (58 ± 27 ml/min/kg vs 30 ± 19 ml/min/kg). Mean arrival time after oral dosing was significantly lengthened by hyperthyroidism (100 ± 38 minutes vs 157 ± 71 minutes).

Clinical Relevance

Hyperthyroidism-induced changes in propranolol pharmacokinetics may signal the need to reduce doses of propranolol when they are orally administered to hyperthyroid cats. (Am J Vet Res 1997;58:398–403)

Free access
in American Journal of Veterinary Research