PubMed Health⌕ Search

Biomedical subjects

R A Sams

Publications and source records attributed to R A Sams.

At least 19 recordsLinked to original sources
PubMed2000

Glucose infusion attenuates endogenous glucose production and enhances glucose use of horses during exercise.

We examined the effects of increased glucose availability on glucose kinetics and substrate utilization in horses during exercise. Six conditioned horses ran on a treadmill for 90 min at 34 +/- 1% of maximum oxygen uptake. In one trial [glucose (Glu)], glucose was infused at a mean rate of 34.9 +/- 1.1 micromol. kg(-1). min(-1), whereas in the other trial [control (Con)] an equivalent volume of isotonic saline was infused. Plasma glucose increased during exercise in Glu (90 min: 8.3 +/- 1.7 mM) but was largely unchanged in Con (90 min: 5.1 +/- 0.4 mM). In Con, hepatic glucose production (HGP) increased during exercise, reaching a peak of 38.6 +/- 2.7 micromol. kg(-1). min(-1) after 90 min. Glucose infusion partially suppressed (P < 0.05) the rise in HGP (peak value 25.8 +/- 3.3 micromol. kg(-1). min(-1)). In Con, glucose rate of disappearance (R(d)) rose to a peak of 40.4 +/- 2.9 micromol. kg(-1). min(-1) after 90 min; in Glu, augmented glucose utilization was reflected by values for glucose R(d) that were twofold higher (P < 0.001) than in Con between 30 and 90 min. Total carbohydrate oxidation was higher (P < 0.05) in Glu (187.5 +/- 8.5 micromol. kg(-1). min(-1)) than in Con (159.2 +/- 7.3 micromol. kg(-1).min(-1)), but muscle glycogen utilization was similar between trials. We conclude that an increase in glucose availability in horses during low-intensity exercise 1) only partially suppresses HGP, 2) attenuates the decrease in carbohydrate oxidation during such exercise, but 3) does not affect muscle glycogen utilization.

Animals↗
PubMed2000

Epinephrine inhibits exogenous glucose utilization in exercising horses.

This study examined the effects of preexercise glucose administration, with and without epinephrine infusion, on carbohydrate metabolism in horses during exercise. Six horses completed 60 min of treadmill exercise at 55 +/- 1% maximum O(2) uptake 1) 1 h after oral administration of glucose (2 g/kg; G trial); 2) 1 h after oral glucose and with an intravenous infusion of epinephrine (0.2 micromol. kg(-1). min(-1); GE trial) during exercise, and 3) 1 h after water only (F trial). Glucose administration (G and GE) caused hyperinsulinemia and hyperglycemia ( approximately 8 mM). In GE, plasma epinephrine concentrations were three- to fourfold higher than in the other trials. Compared with F, the glucose rate of appearance was approximately 50% and approximately 33% higher in G and GE, respectively, during exercise. The glucose rate of disappearance was approximately 100% higher in G than in F, but epinephrine infusion completely inhibited the increase in glucose uptake associated with glucose administration. Muscle glycogen utilization was higher in GE [349 +/- 44 mmol/kg dry muscle (dm)] than in F (218 +/- 28 mmol/kg dm) and G (201 +/- 35 mmol/kg dm). We conclude that 1) preexercise glucose augments utilization of plasma glucose in horses during moderate-intensity exercise but does not alter muscle glycogen usage and 2) increased circulating epinephrine inhibits the increase in glucose rate of disappearance associated with preexercise glucose administration and increases reliance on muscle glycogen for energy transduction.

Adrenergic Agonists↗
PubMed2000

beta-adrenergic blockade augments glucose utilization in horses during graded exercise.

To examine the role of beta-adrenergic mechanisms in the regulation of endogenous glucose (Glu) production [rate of appearance (R(a))] and utilization [rate of disappearance (R(d))] and carbohydrate (CHO) metabolism, six horses completed consecutive 30-min bouts of exercise at approximately 30% (Lo) and approximately 60% (Hi) of estimated maximum O(2) uptake with (P) and without (C) prior administration of the beta-blocker propranolol (0.22 mg/kg iv). All horses completed exercise in C; exercise duration in P was 49.9 +/- 1.2 (SE) min. Plasma Glu was unchanged in C during Lo but increased progressively in Hi. In P, plasma Glu rose steadily during Lo and Hi and was higher (P < 0.05) than in C throughout exercise. Plasma insulin declined during exercise in P but not in C; beta-blockade attenuated (P < 0.05) the rise in plasma glucagon and free fatty acids and exaggerated the increases in epinephrine and norepinephrine. Glu R(a) was 8.1 +/- 0.8 and 8.4 +/- 1.0 micromol. kg(-1). min(-1) at rest and 30.5 +/- 3.6 and 42.8 +/- 4.1 micromol. kg(-1). min(-1) at the end of Lo in C and P, respectively. During Hi, Glu R(a) increased to 54.4 +/- 4.4 and 73.8 +/- 4.7 micromol. kg(-1). min(-1) in C and P, respectively. Similarly, Glu R(d) was approximately 40% higher in P than in C during Lo (27.3 +/- 2.0 and 39.5 +/- 3.3 micromol. kg(-1). min(-1) in C and P, respectively) and Hi (37.4 +/- 2.6 and 61.5 +/- 5.3 micromol. kg(-1). min(-1) in C and P, respectively). beta-Blockade augmented CHO oxidation (CHO(ox)) with a concomitant reduction in fat oxidation. Inasmuch as estimated muscle glycogen utilization was similar between trials, the increase in CHO(ox) in P was due to increased use of plasma Glu. We conclude that beta-blockade increases Glu R(a) and R(d) and CHO(ox) in horses during exercise. The increase in Glu R(d) under beta-blockade suggests that beta-adrenergic mechanisms restrain Glu R(d) during exercise.

Adrenergic beta-Antagonists↗
PubMed2000

Anesthetic, cardiorespiratory, and metabolic effects of four intravenous anesthetic regimens induced in horses immediately after maximal exercise.

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 guaifenesin-thiopental administration than after ketaminediazepam or tilet-amine-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 tilet-amine-zolazepam induced good quality anesthesia with acceptable perturbations in cardiopulmonary and metabolic indices. Ketamine alone and guaifenesin-thiopental regimens are not recommended.

Acepromazine↗
PubMed2000

Pharmacokinetics, pharmacodynamics, and analgesic effects of morphine after rectal, intramuscular, and intravenous administration in dogs.

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.

Administration, Rectal↗
PubMed1999

Testing for therapeutic medications: analytical/pharmacological relationships and limitations' on the sensitivity of testing for certain agents.

Proper veterinary care of horses requires that horses in training have access to modern therapeutic medication. However, the sensitivity of equine drug testing now allows for detection of pharmacologically insignificant concentrations of many therapeutic medications. In 1995, the Association of Racing Commissioners International (ARCI) resolved that members 'address trace level detection so as not to lead to disciplinary action based on pharmacologically insignificant traces of these substances'. The rationale behind this approach is to prevent overly-sensitive testing from inhibiting the proper and appropriate veterinary care of performance horses. This review describes a scientific approach to implement this resolution using local anaesthetics as a model system and compares this approach with others currently in place. For the purpose of this discussion, a 'trace' concentration is defined as a pharmacologically-insignificant concentration. Initially, the target pharmacological effect (e.g. local anaesthesia) was identified, and the dose response relationship was quantified. The 'Highest No Effect Dose' (HNED) was estimated and then administered to horses. Next, the target analyte was identified, synthesized, if necessary, and quantified in blood or urine; the concentrations observed after administration of the HNED are, by definition, true concentrations and hence are pharmacologically insignificant. The key to this approach has been the synthesis of a unique series of authentic equine metabolite standards, which has allowed scientific identification of the concentration at which the pharmacological effect was indistinguishable from control values. Traces found at less than this concentration are, by definition, 'no effect limits', 'no effect traces' (NETs), 'no effect cut-offs', 'no effect limitations on the sensitivity of testing', or 'subtherapeutic residues'. Conversely, this approach will also identify potent medications for which the sensitivity of testing may need to be improved. Within the context of these experiments, the data create an analytical/pharmacological database that should assist industry professionals in interpreting the significance of trace concentrations of these medications or their metabolites in official samples. The most favourable outcome of this research is more medically appropriate use of therapeutic medications in performance horses, yielding substantial benefits to the health and welfare of these horses.

Anesthetics, Local↗
PubMed1999

Detection and identification of flunixin after multiple intravenous and intramuscular doses to horses.

The objectives of the study were to compare various methods to determine flunixin in test samples collected periodically from horses after intramuscular (IM) and intravenous (IV) dosing at the maximum recommended dosage and to document detection times for this drug in test samples. Flunixin, a nonsteroidal anti-inflammatory drug approved for use in horses, was administered to eight mares in five consecutive daily doses of 1.1 mg per kilogram of body weight by the IM or IV route. Flunixin was detected in urine samples collected at various times after drug administration by flunixin enzyme-linked immunosorbent assay (ELISA), thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and gas chromatographic-mass spectrometric (GC-MS) methods. Detection time was defined as the time period over which flunixin was detected and was dependent on the method used. The shortest detection times were 24 to 48 h and were observed when the TLC method was used. On the other hand, detection times were as long as 15 days when HPLC, GC-MS, and flunixin ELISA methods were used. The use of these more sensitive tests to monitor official samples collected from racehorses could result in positive tests for flunixin when it is exerting no detectable clinical effects because it produces clinical effects lasting only 24-36 h in horses.

Animals↗
PubMed1999

Attenuation by phenylbutazone of the renal effects and excretion of frusemide in horses.

The objectives of this study were to determine the effect of phenylbutazone premedication on the pharmacokinetics and urinary excretion of frusemide in horses; and on frusemide-induced changes in urinary electrolyte excretion. Six Standardbred mares were used in a 3-way crossover design. The pharmacokinetics and renal effects of frusemide (1 mg/kg bwt i.v.) were studied with and without phenylbutazone premedication (8.8 mg/kg bwt per os 24 h before, followed by 4.4 mg/kg bwt i.v. 30 min before frusemide administration). A control (saline) treatment was also studied. Administration of frusemide without phenylbutazone led to diuresis, natriuresis, kaliuresis and chloruresis, and altered the ratio of sodium:chloride excretion from 0.4 to 1.0 in the first hour of diuresis. When frusemide and phenylbutazone were administered, sodium and chloride excretion in the first hour were significantly (P<0.05) reduced by 40 and 32%, respectively, when compared to frusemide administrationwithout phenylbutazone. The fractional clearance of sodium and chloride was also significantly reduced. Potassium excretion, potassium fractional clearance and the ratio of sodium to chloride excretion were not affected by administration of phenylbutazone. During peak diuresis, phenylbutazone did not affect the efficiency of frusemide with respect to electrolyte excretion. The plasma disposition of frusemide was not affected by phenylbutazone. However, the renal excretion of frusemide decreased by approximately 25%. We conclude that the decreased urinary excretion of frusemide by phenylbutazone led to an attenuation of frusemide-induced increases in urinary excretion of sodium and chloride. Since the efficiency of frusemide was not affected by phenylbutazone, we conclude that phenylbutazone attenuates the renal excretion of frusemide without inhibiting the intrarenal activity of frusemide in horses.

Animals↗
PubMed1999

Cardiorespiratory and metabolic effects of xylazine, detomidine, and a combination of xylazine and acepromazine administered after exercise in horses.

OBJECTIVE: To determine sedative, cardiorespiratory and metabolic effects of xylazine hydrochloride, detomidine hydrochloride, and a combination of xylazine and acepromazine administered i.v. at twice the standard doses 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 to establish a uniform level of fitness. Each horse ran 4 simulated races, with a minimum of 14 days between races. Simulated races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until they were fatigued or for a maximum of 2 minutes. One minute after the end of exercise, horses were treated i.v. with xylazine (2.2 mg/kg of body weight), detomidine (0.04 mg/kg), a combination of xylazine (2.2 mg/kg) and acepromazine (0.04 mg/kg), or saline (0.9% NaCl) solution. Treatments were randomized so that each horse received each treatment once, in random order. Cardiopulmonary indices were measured, and samples of arterial and venous blood were collected immediately before and at specific times for 90 minutes after the end of each race. RESULTS: All sedatives produced effective sedation. The cardiopulmonary depression that was induced was qualitatively similar to that induced by administration of these sedatives to resting horses and was not severe. Sedative administration after exercise prolonged the exercise-induced increase in body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine, detomidine, or a combination of xylazine-acepromazine at twice the standard doses produced safe and effective sedation in horses that had just undergone a brief, intense bout of exercise.

Acepromazine↗
PubMed1998

The regulation of drugs and medicines in horse racing in the United States. The Association of Racing Commissioners International Uniform Classification of Foreign Substances Guidelines.

The primary reason for developing the ARCI Uniform Classification of Foreign Substances was to give stewards and other racing regulators guidelines to assist them in understanding the relative performance effects and general offensiveness to the Rules of Racing of various drugs and medications. As such, these guidelines have been very useful in the world of racing regulation--officially or unofficially--because this classification system, for the first time, places a relative number on the inappropriateness of any one of more than 750 agents appearing in forensic samples taken from racing horses. The guidelines set up by this system established the first framework for dialogue among veterinary pharmacologists reviewing these drugs. Prior to development of the guidelines, pharmacologists had their own opinions about these agents and their effects on performance. The guidelines, however, established a framework for discussion, and there has been surprising unanimity about the classification of each of these agents. Not only does this classification system provide a useful basis for dialogue among experts, it is also useful for regulators, horsemen and other laymen, most of whom have little training or experience with drugs and their effects on horses. The system is easily understandable and communicates the relative possibility of any classified substance to affect the performance of a horse. Consequently, the system has made it possible for laymen to understand the degree of impropriety of all drugs and medicines with which they may have contact. Grouping a large number of drugs into specific classes has greatly facilitated discussion about regulations and penalties, and the classification system is related to proposed penalty guidelines which were developed in parallel. With regard to penalties for Class 1 agents, it is easy to assign and defend substantial penalties after examining the guideline statement describing the possible performance effects of this group of agents as well as the fact that they have no well recognized therapeutic role. Similarly, the relatively modest effects of class 4 and 5 agents, combined with the fact that these groups encompass a large number of well recognized therapeutic agents, helps in understanding the possible presence of trace levels of these agents in post-race samples. In summary, the ARCI Uniform Classification of Foreign Substances Guidelines condenses data on drugs and medications and places them into a simple five class system. This system has made it possible to confidently discuss the regulatory implications of the identification of any one of the approximately 750 classified substances potentially found in forensic samples from a performance horse. As such it facilitates both the development and implementation of more understandable and equitable regulatory processes.

Animals↗
PubMed1998

The pharmacokinetics of furosemide in anaesthetized horses after bilateral ureteral ligation.

The pharmacokinetics of furosemide were investigated in anaesthetized horses with bilateral ureteral ligation (BUL) with (n = 5) or without (n = 5) premedication with phenylbutazone. Horses were administered an intravenous (i.v.) bolus dose of furosemide (1 mg/kg) approximately 60-90 min after BUL. Plasma samples collected up to 3 h after drug administration were analysed by a validated high performance liquid chromatography method. Median plasma clearance (CLp) of furosemide in anaesthetized horses with BUL was 1.4 mL/min/kg. Apparent steady state volume of distribution (Vd(ss)) ranged from 169 to 880 mL/kg and the elimination half life (t1/2) ranged from 83 min to 209 h. No differences in plasma concentration or kinetic parameter estimates were observed when phenylbutazone was administered before furosemide administration. BUL markedly reduces the elimination of furosemide in horses and models the potential effects that severe changes in kidney function may have on drug kinetics in horses.

Animals↗
PubMed1998

Chronic phenobarbital therapy reduces plasma benzodiazepine concentrations after intravenous and rectal administration of diazepam in the dog.

Disposition of diazepam (DZ) 2 mg/kg after single bolus intravenous (i.v.) and rectal (p.r.) administration before and after 30 day oral phenobarbital therapy was investigated in normal dogs. Adverse cardiovascular and neurologic effects for each drug, dosage and route of administration were evaluated. Plasma benzodiazepine concentrations were determined by fluorescence polarization immunoassay. This assay measured DZ and its active metabolites, oxazepam and nordiazepam to provide a total benzodiazepine concentration. Mean peak plasma concentrations after i.v. administration were 5963 and 5565 ng/mL, before and after phenobarbital treatment, respectively. After p.r. administration, mean peak concentrations were 629 ng/mL and 274 ng/mL and were reached within 30 min before and after phenobarbital treatment, respectively. The target concentration for potential seizure control (i.e. 150 ng/mL) was attained in five dogs in the post phenobarbital p.r. group with a median time to attainment of target concentration of 8 min. The administration of phenobarbital resulted in significantly lower areas under the plasma concentration vs. time curves (AUC) for both i.v. and p.r. administration. Similarly, there was a reduction in maximal plasma concentration, bioavailability (F), mean residence time, and time to target and peak concentrations in the postphenobarbital p.r. group, as compared to the prephenobarbital p.r. group. Adverse cardiovascular and neurologic effects were short-lived and were considered of minor clinical significance. Overall, chronic phenobarbital therapy in the dog reduces total benzodiazepine concentration after i.v. and p.r. administration presumably due to increased hepatic clearance of DZ and its metabolites oxazepam and nordiazepam. Despite this finding, administration of DZ rectally at 2 mg/kg may be a clinically useful alternative to i.v. administration to treat emergency seizures when i.v. therapy is not possible in dogs on chronic phenobarbital therapy.

Administration, Oral↗
PubMed1998

Absence of detectable pharmacological effects after oral administration of isoxsuprine.

Isoxsuprine is reported to be a peripheral vasodilator used in human and veterinary medicine to treat ischaemic vascular disease. In horses, it is generally administered orally to treat navicular disease and other lower limb problems. To define the scope and duration of its pharmacological responses after oral administration, 6 horses were dosed with isoxsuprine HCl (1.2 mg/kg bwt) q. 12 h for 8 days and then tested to assess the duration and extent of pharmacological actions. There was no significant difference between isoxsuprine and control treatment values for heart rate, spontaneous activity, sweat production, anal muscle tone, core and skin temperatures, and cutaneous blood flow. The lack of pharmacological effect following oral administration was in sharp contrast to the marked response following i.v. dosing reported in earlier experiments.

Administration, Oral↗
PubMed1998

Exercise-training-induced alterations in hepatic function in mares.

The effects of exercise training on hepatic function in horses were determined by studying the plasma clearance of antipyrine (20 mg/kg iv) in adult mares that either underwent treadmill training for 5 wk (n = 7) or remained in box stalls for the same time period (n = 6). Training consisted of treadmill exercise at 60% (12 min/day) and 90% (3 min/day) of pretraining maximal oxygen consumption (V(O2)max) for 6 days/wk for 5 wk. V(O2)max and velocity to obtain a blood lactate concentration of 4 mmol/l were significantly increased (from 129 to 149 ml x min-1 x kg-1 and from 5.6 to 6.1 m/s, respectively) as a result of training. The plasma clearance and volume of distribution of antipyrine increased significantly in the trained group (from 5.5 to 6.4 ml x min-1 x kg-1 and from 813 to 881 ml/kg, respectively) and decreased significantly in the untrained group. Elimination half-lives did not change as a result of training or box rest. Increases in plasma antipyrine clearance were indicative of an increase in hepatic metabolism of antipyrine. Increases in the volume of distribution of antipyrine suggest that total body water increases as a result of exercise training.

Animals↗
PubMed1998

Antipyrine pharmacokinetics and urinary excretion in female horses.

OBJECTIVE: To measure renal clearance of antipyrine and urinary excretion of antipyrine (AP) metabolites in horses by use of validated high-performance liquid chromatography (HPLC) methods. ANIMALS: 8 Standardbred mares. PROCEDURE: HPLC methods for measurement of AP in equine plasma and AP and its metabolites in equine urine were validated. Antipyrine (20 mg/kg of body weight) was administered i.v., and blood samples and urine specimens were collected over 24 hours. RESULTS: Median plasma clearance of AP in horses was 6.2 ml/min/kg, of which < 2% could be attributed to renal clearance. Urinary excretion of AP and its metabolites over 24 hours accounted for < 22% of the AP dose administered. The major metabolite of AP in urine was 4-hydroxyantipyrine. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the proven validated methods for measuring AP and its metabolites indicated that AP has minimal renal clearance in horses, suggesting that plasma clearance of AP reflects hepatic clearance. Combined with AP metabolite data, the pharmacokinetics of AP may be useful for assessment of hepatic cytochrome P450 activity in horses.

Animals↗
PubMed1998

Pharmacokinetics of ketoprofen in healthy foals less than twenty-four hours old.

OBJECTIVE: To determine pharmacokinetic variables that describe disposition of ketoprofen after its i.v. 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 i.v. 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.

Aging↗
PubMed1998

Pharmacokinetics of multiple-dose administration of eltenac in horses.

OBJECTIVE: To compare pharmacokinetics of eltenac after first and last IV administrations (0.5 mg/kg), using a multiple dosing schedule. ANIMALS: 6 adult mares. PROCEDURE: Eltenac (50 mg/ml) was administered IV at a dosage of 0.5 mg/kg of body weight every 24 hours for days 0 through 4. On days 0 and 4, blood samples were collected before, then periodically for 8 hours after eltanac administration. Concentration of eltenac in plasma samples was determined by use of high-performance liquid chromatography. RESULTS: On day 0, median area under the plasma eltenac concentration versus time curve (AUC) was 6.77 microg.h/ml (range, 5.61 to 8.08 microg.h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.03 to 1.40 ml/min/kg), and median steady-state volume of distribution was 191 ml/kg (range, 178 to 218 ml/kg). Median terminal half-life of eltenac was 2.36 hours (range, 2.30 to 2.98 hours). On day 4, median eltenac AUC was 6.70 microg.h/ml (range, 5.21 to 7.44 microg.h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.12 to 1.53 ml/min/kg), and median steady-state volume of distribution was 193 ml/kg (range, 172 to 205 ml/kg). Median terminal half-life of eltenac was 2.40 hours (range, 2.11 to 3.25 hours). Protein binding of eltenac, determined by ultrafiltration, was > 99% at a total plasma concentration of 36 microg/ml. CONCLUSION: Pharmacokinetic variables determined for each horse were not different between days 0 and 4. CLINICAL RELEVANCE: Under conditions of this study, there was no clinically relevant accumulation of eltenac in equine plasma or alteration of pharmacokinetic variables after multiple IV dosing of 0.5 mg/kg of eltenac.

Aniline Compounds↗