Biomedical subjects

K W Hinchcliff

Publications and source records attributed to K W Hinchcliff.

At least 55 records · Page 3Linked to original sources

PubMed1999

Frusemide and weight carriage alter the acid:base responses of horses to incremental and to brief intense exertion.

We speculated that frusemide would attenuate the acidosis associated with intense exertion, and that weight carriage would mitigate this effect. Therefore, in each of 2 experiments we measured pulmonary artery and systemic arterial blood pH, PCO2, PO2 and pulmonary artery temperature in 9 horses during exertion on a treadmill after each of 3 treatments. The treatments were: 1) injection of saline solution (C), 2) injection of frusemide (1 mg/kg bwt, i.v. 4 h before running) (FU) and 3) injection of frusemide (F) as for FU and the horses carried weight equal to that lost in the 4 h after frusemide administration (FL). In Experiment 1 the horses performed an incremental exercise test of 90 s at each of 4, 7 and 9 m/s (4 degrees incline). In Experiment 2, the horses ran on a treadmill inclined at 4 degrees for 3 min at 3 m/s, at approximately 120% VO2max for 2 min, and 3 m/s for 5 min. Blood samples for measurement of blood pH, PCO2 and PO2 were collected into heparinised glass syringes. Values were adjusted for changes in pulmonary artery blood temperature. Data were analysed using a 2 way repeated measures ANOVA. There was a consistent pattern in both experiments characterised by a mild alkalosis or mitigated acidosis, compared to C, at rest and during exercise and recovery after FU (P < 0.05). Weight carriage blunted or inhibited the effect of frusemide during exercise and recovery. In experiment 2, at the end of the sprint, FU treatment resulted in a less severe acidosis than did C or FI: mixed venous pH for C, FU, and FL at the end of the sprint were 6.93, 6.98 and 6.93, respectively (P interaction = 0.038), mixed venous base excess was -12.4, -9.91, and -11.8 mmol/l, respectively, and arterial base excess of -1.44, -12.7 and -14.1 mmol/l (P interaction = 0.006) respectively. These effects persisted into recovery. A similar pattern of responses occurred during the incremental exercise test, with weight carriage offsetting the alkalinizing effect of frusemide. We conclude that frusemide attenuates the acidosis of intense exertion and that carriage of weight prevents this effect.

Acid-Base Equilibrium↗

PubMed1999

Effect of ambient temperature and humidity on pulmonary artery temperature of exercising horses.

Six healthy Thoroughbred mares were trained to run on a high-speed treadmill and were conditioned for approximately 5 weeks. Each horse performed 6 identical standardised exercise tests (SET) 5 to 7 days apart. Each SET was performed under different ambient laboratory conditions: low temperature/low humidity (LL) 20.2 degrees +/- 0.6 degree C, 53.6 +/- 4.1%; low temperature/high humidity (LH) 19.7 +/- 0.6 degrees C, 86.7 +/- 4.2%; medium temperature/low humidity (ML) 24.6 +/- 0.2 degrees C, 58.7 +/- 3.7%; medium temperature/high humidity (MH) 24.7 +/- 0.3 degrees C, 87.5 +/- 1.4%; high temperature/low humidity (HL) 31.1 +/- 0.6 degrees C, 41.6 +/- 3.5%; and high temperature/high humidity (HH) 30.6 +/- 0.2 degrees C, 84.4 +/- 3.6%. Horses completed the 46 min SET, became fatigued or exercise was terminated when a pulmonary artery temperature (PAT) of 41.5 degrees C was reached. During a 30 min recovery period, horses stood quietly on the treadmill. Only one trial was terminated due to fatigue; in all other trials horses completed the 46 min SET or the trial was terminated when PAT = 41.5 degrees C. The relationships among run time (min) or PAT (degree C), ambient temperature and % relative humidity were defined by multiple linear regression analysis. Run time (min) = 90.9 - (1.39 x ambient temperature degree C) - (0.236 x relative humidity %). Approximately 54% of the variation in run times was explained by variation in environmental conditions, indicating that ambient temperature and humidity contribute substantially to the rate of rise in PAT. Run times to a PAT of 41.5 degrees C were significantly shorter (P < 0.000001) in HH than in other groups during the SET. Approximately 63% of the variation in PAT at the end of exercise was due to ambient temperature and humidity. In general, the longer the exercise time, the better the correlation among PAT, ambient temperature and relative humidity. Rectal temperature increased significantly (P < 0.0001) during the recovery period only in horses in the HH group, indicating that heat dissipation during recovery may have been impaired by environmental conditions. This study demonstrates that hot humid conditions result in more rapid rate of rise in PAT for horses undertaking identical exercise tests.

Animals↗

PubMed1999

Hyperbolic relationship between time-to-fatigue and workload.

The power:time-to-fatigue relationship for high-intensity exercise in man is useful in determining anaerobic work capacity. The purpose of this study was to determine the nature of this relationship in horses. Eight Standardbred horses performed 5 or 6 run-to-fatigue trials on a treadmill. Exercise intensities were chosen to induce fatigue in 30 to 240 s. The order of trials was randomised for each horse, but balanced overall for the first 4 trials. The data for power (independent variable) and time-to-fatigue (dependent variable) were tested for goodness of fit to hyperbolic, linear and exponential equations by nonlinear regression. The best fit to the data was obtained using the hyperbolic relationship t = W'(P- phi PA) where t is the time to fatigue, W' is the anaerobic work capacity, P is the power and phi PA is the critical power value. The values for W' and phi PA were 47,000 +/- 500 J and 2490 +/- 150 watts, respectively. We conclude that the power:time-to-fatigue relationship of horses is hyperbolic and that this relationship may be useful in assessing anaerobic capacity of horses.

Animals↗

PubMed1999

Effects of prior exercise on muscle metabolism during sprint exercise in horses.

The effect of warm-up exercise on energy metabolism and muscle glycogenolysis during sprint exercise (Spr) was examined in six fit Standardbred horses exercised at 115% of maximal O(2) consumption (VO(2 max)) until fatigued, 5 min after each of three protocols: 1) no warm-up (NWU); 2) 10 min at 50% of VO(2 max) [low-intensity warm-up (LWU)]; and 3) 7 min at 50% VO(2 max) followed by 45-s intervals at 80, 90, and 100% VO(2 max) [high-intensity warm-up (HWU)]. Warm-up increased (P < 0.0001) muscle temperature (T(m)) at the onset of Spr in LWU (38.3 +/- 0.2 degrees C) and HWU (40.0 +/- 0. 3 degrees C) compared with NWU (36.6 +/- 0.2 degrees C), and the rate of rise in T(m) during Spr was greater in NWU than in LWU and HWU (P < 0.01). Peak VO(2) was higher and O(2) deficit lower (P < 0. 05) when Spr was preceded by warm-up. Rates of muscle glycogenolysis were lower (P < 0.05) in LWU, and rates of blood and muscle lactate accumulation and anaerobic ATP provision during Spr were lower in LWU and HWU compared with NWU. Mean runtime (s) in LWU (173 +/- 10 s) was greater than HWU (142 +/- 11 s) and NWU (124 +/- 4 s) (P < 0. 01). Warm-up was associated with augmentation of aerobic energy contribution to total energy expenditure, decreased glycogenolysis, and longer run time to fatigue during subsequent sprint exercise, with no additional benefit from HWU vs. LWU.

Adenosine Triphosphate↗

PubMed1999

Evaluation of washing with cold water to facilitate heat dissipation in horses exercised in hot, humid conditions.

OBJECTIVE: To determine whether body temperature of horses exercised in hot, humid conditions and then repetitively washed with cold water will decrease more rapidly than that of horses that are not washed, and to determine whether washing with cold water has deleterious effects on horses. ANIMALS: 5 physically fit Thoroughbred mares, 3 to 10 years old. PROCEDURES: Horses were exercised on a high-speed treadmill in hot (31.1+/-0.3 C), humid (relative humidity, 77.7+/-2%) conditions. Exercise was terminated when pulmonary artery temperature reached 41.5 C. Values for pulmonary artery, rectal, and left gluteal muscle temperatures were compared throughout a 30-minute recovery period after exercise during which horses stood quietly (passive cooling) or were cooled (active cooling) by repeated applications of cold (1 5.6+/-0.6 C) water. RESULTS: Pulmonary artery temperature was significantly less for actively cooled horses, compared with passively cooled horses 4 minutes into the recovery period. Left gluteal muscle temperature decreased significantly in actively cooled, but not passively cooled, horses during the recovery period. Heart rate and rectal temperature were significantly less for actively cooled horses by 15 minutes of the recovery period. Cooling technique did not effect hydration status, muscle health, or serum electrolyte concentrations. Active cooling did not cause obvious adverse effects. CONCLUSION AND CLINICAL RELEVANCE: Active cooling by washing with cold water is a safe, effective means for facilitating heat dissipation of horses after exercise in a hot, humid environment.

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

Effect of distance traveled and speed of racing on body weight and serum enzyme activity of sled dogs competing in a long-distance race.

OBJECTIVE: To determine the relationship of serum biochemical values and change in body weight with finishing status (retired from or finished the race), finishing order of a team, and distance traveled for dogs participating in a long-distance sled dog race. ANIMALS: 262 of 848 dogs that participated in the 1995 Iditarod Trail sled dog race. DESIGN: Prospective study. PROCEDURE: Body weight was recorded for 261 dogs before the race and again when these dogs retired from or completed the race. Using a nonrandom convenience sample of participating dogs, blood samples were obtained from 151 dogs that retired from the race and 111 dogs that completed the race. RESULTS: Serum biochemical indices of skeletal muscle damage were significantly higher in dogs retiring during the first 500 miles of the race than in dogs retiring in the last 638 miles or finishing the race. Serum sodium concentration was less than the reference range in a significantly greater proportion of dogs that retired from the race than of dogs that completed the race. There was little relationship between finishing order and serum biochemical values. Dogs completing the race lost a mean of 8.9% of body weight, and amount of weight lost was not related to finishing order. CLINICAL IMPLICATIONS: Results indicated that exertional rhabdomyolysis develops more often in dogs that retire during the initial 500 miles of a long-distance race, compared with dogs that complete the race. There is no detectable relationship between the speed with which the race is run (finishing order) and body weight loss or serum biochemical values.

Animals↗

PubMed1998

Congenital defects in newborn foals of mares treated for equine protozoal myeloencephalitis during pregnancy.

Three weak, recumbent neonatal foals with skin lesions, including a thin wooly coat, were born to mares being treated for equine protozoal myeloencephalitis. Mares received sulfadiazine or sulfamethoxazole-trimethoprim, pyrimethamine, folic acid, and vitamin E orally. Foals were anemic, leukopenic, azotemic, hyponatremic, and hyperkalemic. Serum folate concentrations in the 3 foals and 2 mares were lower than those reported in the literature for clinically normal brood mares. Treatment was unsuccessful. For each foal, necropsy revealed lobulated kidneys with thin cortices and a pale medulla, and the spleen and thymus were small. Histologic examination revealed marked epidermal necrosis without inflammatory cells, thin renal cortices, renal tubular nephrosis, lymphoid aplasia, and bone marrow aplasia and hypoplasia. These observations indicate that oral administration of sulfonamides, 2,4-diaminopyrimidines (pyrimethamine with or without trimethoprim), and folic acid to mares during pregnancy is related to congenital defects in newborn foals.

Abnormalities, Multiple↗

PubMed1998

Erythroid hypoplasia and anemia following administration of recombinant human erythropoietin to two horses.

A Standardbred gelding and a colt were examined because of poor performance and anemia. Each horse had been given recombinant human erythropoietin (rhEPO; 4,000 IU) at least twice within the preceding 2 to 4 months. The horses had an Het of 16 and 24%, serum iron concentrations of 210 and 304 micrograms/dl (reference range, 73 to 140 micrograms/dl), total iron binding capacities of 239 and 321 micrograms/dl (reference range, 266 to 364 micrograms/dl), values for the percentage saturation of transferrin by iron of 87.9 and 94% (reference range, 20 to 52%), and serum ferritin concentrations of 255 and 355 ng/ml (reference range, 43 to 261 ng/ml), respectively. There was no clinical or laboratory evidence of immune-mediated hemolysis or an infectious or inflammatory cause of the anemia. Examination of sternebral marrow biopsy specimens revealed generalized bone marrow hypoplasia; myeloid-to-erythroid ratios were 6.7 and 3.2. Moderate-to-marked erythroid hypoplasia was diagnosed in both horses. Compared with serum from a healthy control horse, serum from the affected horses inhibited rhEPO-induced proliferation of erythroid progenitors in vitro. Results suggested that the horses had developed anti-rhEPO antibodies that cross-reacted with endogenous erythropoietin, thereby inhibiting erythropoiesis. Horses were discharged with instructions that rhEPO administration be discontinued and that dexamethasone be administered. Five months later, both horses were back in training. For 1 horse, Hct had increased to 35%, and the other horse was not available for examination.

Anemia↗

PubMed1998

Treatments affecting fluid and electrolyte status during exercise.

A number of feeding and management practices, dietary electrolyte supplements, and medications may affect fluid and electrolyte status in resting and exercising horses. The contents of the gastrointestinal tract of the equine athlete, unlike its human counterpart, are responsible for more than 10% of body weight. Although ingesta traditionally has been considered dead weight for the sprinting horse, it is a valuable reservoir of fluid and electrolytes that may be used during endurance exercise. Numerous strategies for hyperhydration of the equine athlete and for replacement of fluid and electrolytes lost via sweating were developed in preparation for competing in the hot and humid climate of the 1996 Olympic Games in Atlanta. These strategies have implications for all equine athletes. Medications, including sodium bicarbonate, furosemide, and acetazolamide commonly are used to enhance performance by either buffering alterations in fluid and electrolyte homeostasis or by ameliorating the effects of other conditions that may limit performance.

Acetazolamide↗

PubMed1998

Catecholamine and cortisol responses of horses to incremental exertion.

The responses of the plasma concentrations of catecholamines and cortisol in horses to varied relative intensities of exertion were examined. The plasma concentrations of cortisol, epinephrine and norepinephrine increased significantly (p < 0.05) with exertion. The plasma cortisol concentrations at relative work intensities of 48.3% +/- 1.4%, 82.3% +/- 2.0% and 99.6% +/- 0.4% of VO2max were 114%, 124%, and 126%, respectively, of those at rest, whereas the plasma epinephrine concentrations were 239%, 772% and 3483%, and the norepinephrine concentrations were 138%, 255%, and 1121% of the values at rest. There was a significant (p < 0.0001) relationship between the plasma epinephrine and norepinephrine concentrations. The blood lactate concentration and the plasma epinephrine and norepinephrine concentrations were significantly (p < 0.0001) related, as were the relative work intensity (%VO2max) and the plasma epinephrine and norepinephrine concentrations. The relationships between the plasma cortisol concentration and work intensity or blood lactate concentration were not significant (p > 0.05). This study demonstrates a relationship between work intensity and indicators of adrenal medullary and sympathetic activity during brief exertion in horses.

Adrenal Medulla↗

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

Fluid administration attenuates the haemodynamic effect of frusemide in running horses.

The effect of blood volume repletion after frusemide administration on the right atrial and pulmonary artery pressure responses of horses to exercise has not been reported. We examined right atrial and pulmonary artery pressure and plasma atrial natriuretic peptide concentration (ANP) responses to an incremental exercise test in 6 Standardbred mares. Horses were treated, in a 3 way cross over design, with isotonic saline, frusemide (1 mg/kg bwt, i.v.), and frusemide followed 3 h later by lactated Ringer's solution (12 ml/kg bwt, i.v.). Three and a half hours after saline or frusemide administration the horses completed a standard exercise test. Frusemide significantly affected the right atrial and pulmonary artery pressure and ANP responses to exercise. Fluid administration decreased plasma total protein concentrations at rest and during running and abolished the effects of frusemide on the haemodynamic and ANP responses to exercise. These results suggest that the haemodynamic effect of frusemide in running horses is mediated, in large part, by a reduction in plasma and blood volume.

Animals↗

PubMed1998

Effect of moderate exercise on the severity of clinical signs associated with influenza virus infection in horses.

The purpose of this experiment was to determine if exercising horses, infected with influenza virus, exacerbates the severity of clinical disease. Eight horses were trained on a treadmill for 42 days and then challenged with aerosolised influenza A/equine/Kentucky/91 (H3N8). Following challenge, 4 horses (exercise group) continued training for 28 days, while the other 4 horses (nonexercise group) were confined to their stalls. All horses developed clinical signs within 36 h of challenge (fever, coughing, and mucopurulent nasal discharge) and clinical scores were greater in the exercise group. Horses developed fever from Days 1-11 post challenge (PC) and were tachypnoeic and tachycardic from Days 1-14 PC. All horses lost weight within 4 days PC, but the exercise group lost an average of 20 kg more than the nonexercise group. All horses developed pneumonia, and ultrasonography revealed pulmonary consolidation and oedema by Day 7 PC that was resolving by Day 14 PC. Endoscopy and transtracheal aspirates showed airway inflammation for up to 21 days PC. While the exercise group exhibited more severe signs of clinical disease, resolution occurred for both groups on approximately Day 14 PC, and no adverse effects were noted at the end of the study. However, the potential long term effects of exercising horses acutely infected with influenza virus are unknown. Until further research is conducted in this area, it appears prudent not to exercise affected horses.

Analysis of Variance↗

PubMed1998

Effect of tryptophan and of glucose on exercise capacity of horses.

We hypothesized that central fatigue may have a role in limiting the endurance capacity of horses. Therefore, we tested the effect of infusing tryptophan and/or glucose on endurance time and plasma concentrations of free tryptophan and other substrates thought to affect tryptophan uptake into the brain of seven mares (3-4 yr of age, 353-435 kg) that ran on a treadmill at 50% of maximal O2 consumption to fatigue. With use of a counterbalanced crossover design, the horses were infused with tryptophan (100 mg/kg in saline solution) or a similar volume of saline solution (placebo) before exercise. During exercise, horses received infusions of glucose (2 g/min, 50% wt/vol) or a similar volume of saline. Thus the treatments were 1) tryptophan and glucose (T & G), 2) tryptophan and placebo (T & P), 3) placebo and glucose (P & G), and 4) placebo and placebo (P & P). Mean heart rate, hematocrit, and concentration of plasma total solids before and during exercise were similar for all trials. Mean time to exhaustion was reduced (P < 0.05) for T & P and T & G compared with P & P [86.1 +/- 6.9 and 87.1 +/- 6.8 vs. 102.3 +/- 10.3 (SE) min], whereas endurance for P & G (122.4 +/- 11.9 min) was greater than for all other trials (P < 0.05). Compared with nontryptophan trials, during the tryptophan trials plasma prolactin increased (P < 0.05) nearly threefold before exercise and almost twofold early in exercise. Muscle glycogen concentrations were reduced (P < 0.05) below preexercise values in the P & G and P & P trials only. However, glucose infusions (P & G) did not affect (P > 0.05) concentrations of plasma free fatty acids or ratios of branched-chain amino acids to free tryptophan. In conclusion, tryptophan infusion reduced endurance time, which was consistent with the central fatigue hypothesis. The failure of glucose infusion to alleviate the effects of tryptophan and the absence of significant muscle glycogen reduction in the tryptophan trials suggest that the early onset of fatigue in the tryptophan trials is not due to a lack of readily available substrate.

Animals↗

PubMed1998

Effect of endurance training on cardiac morphology in Alaskan sled dogs.

The cardiac morphology of 77 conscious Alaskan sled dogs before and after 5 mo of endurance training (20 km/day team pulling a sled and musher) was studied using two-dimensional and M-mode echocardiography. Subgroups included dogs with at least one season of previous training ("veterans") and dogs undergoing their first season of training ("rookies"). Training resulted in a significant (P < 0.05) decrease in resting heart rate (-15%) and significant increases in interventricular septal thickness (systole, 15%; diastole, 13%), left ventricular (LV) internal dimension in diastole (LVIDd, 4%), LV free wall thickness in systole (9%) and diastole (LVWd, 9%), and left atrial diameter (5%) in all dogs, but the increase in LVWd was greater in rookies (16%) than in veterans (7%). Training increased end-diastolic volume index (8%), LV mass index (24%), and heart weight index (24%) and decreased the LVIDd-to-LVWd ratio (-6%) but did not alter cardiac index. We conclude that increased LV mass attributable to LV dilation and hypertrophy is associated with endurance training in Alaskan sled dogs. Disproportionate LV wall thickening accompanying LV dilation suggests that cardiac morphological changes are due to volume and pressure loading. These training-induced changes are similar to those documented in human athletes undergoing combined isometric and isotonic training and differ from studies of dogs trained on treadmills.

Alaska↗

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↗