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Topic:Metabolites
Metabolites are small molecules involved in the metabolic processes within a horse's body. They are the intermediates and products of metabolism, encompassing a wide range of compounds, such as amino acids, lipids, carbohydrates, and nucleotides. These molecules play roles in energy production, growth, and cellular repair. The study of equine metabolites, often conducted through metabolomics, provides insights into the physiological and pathological states of horses. Changes in metabolite levels can indicate alterations in metabolic pathways, potentially reflecting health conditions or responses to environmental factors. This page compiles peer-reviewed research studies and scholarly articles that explore the identification, function, and diagnostic potential of metabolites in equine health.
The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies. Six ponies were used to investigate the effect of tolazoline antagonism of detomidine on physiological responses, behavior, epinephrine, norepinephrine, cortisol, glucose, and free fatty acids in awake ponies. Each pony had a catheter inserted into a jugular vein 1 hour before beginning the study. Awake ponies were administered detomidine (0.04 mg/kg intravenously [i.v.]) followed 20 minutes later by either tolazoline (4.0 mg/kg i.v.) or saline. Blood samples were drawn from the catheter 5 minutes before detomidine administration (baseline), 5 minutes after detomidine administration, 20 minute...
Preileal digestibility of coconut fat and soybean oil in horses and their influence on metabolites of microbial origin of the proximal digestive tract. Three horses (approximately 190 kg BW) fitted with a permanent fistula at the end of the jejunum were used. To a control diet (1/3 hay, 2/3 mixed feed) one of two fat types (coconut fat or soybean oil) were added at 2 levels resulting in fat intakes of 0.1 g (control diet) to 0.5 or 1 g/kg BW 0.5 d, respectively. Each experimental period consisted of 2 weeks adaptation, 2 days of breath tests (before and hourly after the morning meal) and 5 days sampling of chyme. Crude fat, crude protein, concentrations of organic acids (SCFA, lactic acid), pH, and the minerals calcium, magnesium and phosphor...
The effect of inflammation on the disposition of phenylbutazone in thoroughbred horses. The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study (n = 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg (n = 5) or 4.4 mg/kg (n = 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. ...
Studies into aromatase activity associated with fetal allantochorionic and maternal endometrial tissues of equine placenta. Identification of metabolites by gas chromatography mass spectrometry. Maternal endometrial and fetal allantochorionic tissues were separated manually from the placentae of seven healthy thoroughbred and three pony mares, ranging in gestational age from 100 to 318 days. The homogeneity of subcellular fractions prepared from these tissues was assessed initially using the marker enzymes, succinate dehydrogenase, NADPH cytochrome C reductase and lactate dehydrogenase for the mitochondrial, microsomal and cytosolic fractions, respectively. Light microscopy and histochemical analysis demonstrated that the separated fetal allantochorionic membrane, which is made up of ...
Solid-phase extraction and derivatisation methods for beta-blockers in human post mortem whole blood, urine and equine urine. This paper details various rapid and sensitive methods for the extraction and derivatisation of propranolol, metoprolol, sotalol, atenolol, pindolol, timolol, oxprenolol, alprenolol and penbutolol in equine urine and in human post mortem whole blood and urine. Three solid-phase extraction methods are described involving the use of either XtrackT XRDAH515, Bond Elut Certify or Sep-Pak C18 cartridges. Two derivatisation methods are also described involving the formation of cyclised silyl or pentafluoropropionate derivatives with either chloromethyldimethylchlorosilane or pentafluoropropionic anh...
Theoretical relationship between the post-administration time and plasma or urinary concentration of a metabolite and the unchanged drug. Administration of caffeine to horses. In a doping test for racing horses, it is useful for the elucidation of the illegal use of drugs if one can estimate the time at which the detected drug was administered. In order to estimate the time which has elapsed after the administration of caffeine (CA) into horses, the ratios of concentration for the respective metabolites to the unchanged CA in the plasma or the urine were determined. These ratios have been known to be independent of the dose of CA. The relationship between [plasma or urinary concentration of a metabolite]/ [plasma or urinary concentration of the unchanged drug] and t...
Determination of phase II drug metabolites in equine urine by micellar electrokinetic capillary chromatography. Micellar electrokinetic capillary chromatography (MECC) using diode array detection has been investigated for the determination of phase I and phase II metabolites of drugs in biofluids. Methods were optimised for the determination of morphine, morphine-3-glucuronide, morphine-6-glucuronide, normorphine, meclofenamic acid and its metabolites in equine urine. Solid-phase extraction procedure were developed to concentrate and purify the analytes from spiked and post administration urines for MECC analysis. A simple on-line procedure for monitoring the kinetics of hydrolysis of morphine-glucuroni...
Disposition of human drug preparations in the horse. V. Orally administered oxprenolol. Urinary concentrations of the beta-antagonist oxprenolol and some of its major human metabolites were determined following oral administration of a dose of 160 mg to five fasted horses. Quantitation was performed by gas chromatography-mass spectrometry (GC-MS) in the selected ion mode (SIM) by monitoring ion m/z 466 of the heptafluorobutyric derivatives. As early as 2 h after dosage oxprenolol could be detected in hydrolysed urine and remained detectable up to 24 h. Maximum urinary concentrations and excretion rates were obtained between 2 and 12 h. After 12 h only 2.8% of the administered dos...
Dietary protein and energy restriction in mares: rapid changes in plasma metabolite and hormone concentrations during dietary alteration. Two diets consisting of bermudagrass hay and a corn-cottonseed hull-based supplement were formulated to provide either 100% (control) or 50% (restricted) of the protein and energy requirements for maintenance for mature mares. Twelve light horse mares were fed the control diet for 7 d, and then at 0800 on d 0, six mares were switched to the restricted diet. All diets were fed as two equally sized meals at 0800 and 1600. At 0800 on d 7, mares receiving the restricted diet were switched back to the control diet. Relative to control mares, mares switched to the restricted diet had reduced plasma ...
Detection of quinine and its metabolites in horse urine by gas chromatography-mass spectrometry. After oral administration of quinine sulfate to a thoroughbred mare, seven urine samples were obtained over a 45.5 h period. Using gas chromatography -electron impact ionization and positive-ion chemical ionization mass spectrometry, quinine and five putative metabolites were detected and tentatively identified in enzyme-hydrolysed post-administration urine; all metabolites involved some form of oxidation. The parent drug could be detected for about 16 h and some phase I biotransformation products for up to 40 h post-administration.
[Kidney function tests in horses–methods and reference values in healthy animals]. Investigations of renal function have been done on the basis of renal clearance (Clr) and excretion (E) of endogenous creatinine in healthy horses of different body weight (23 female, 7 male). Creatinine was measured by enzymatic PAP-method. Creatinine-E of female horses was poor positively correlated with body weight. The creatinine-Clr was highly correlated with the inulin-Clr (r = 0,896, p < 0,001). The excretion of creatinine was 35% higher than the filtration of creatinine, determined by inulin-Clr. That demonstrate a tubular net secretion of 26% of the total creatinine excretion. Howe...
Disposition and excretion of 6-methoxy-2-naphthylacetic acid, the active metabolite of nabumetone in horses. To examine, in horses, the disposition and excretion of the active metabolite 6-methoxy-2-naphthylacetic acid (6MNA) of the nonsteroidal anti-inflammatory prodrug nabumetone. Methods: Pharmacokinetic analysis of 6MNA after oral administration of nabumetone and IV administration of 6MNA. Methods: Using a crossover design, 5 horses were orally administered 3.7 mg of nabumetone/kg of body weight. After a 3-week washout period, 4 horses were administered 2.5 mg of 6MNA/kg, IV. Results: Absorption of nabumetone from the gastrointestinal tract and its metabolism to 6MNA had a median appearance half-...
Plasma, urine, and synovial fluid disposition of methylprednisolone acetate and isoflupredone acetate after intra-articular administration in horses. OBJECTIVE--To document plasma, urine, and synovial fluid disposition of 2 common intra-articularly administered steroid preparations, methylprednisolone acetate (MPA) and isoflupredone acetate (IPA). DESIGN--Descriptive investigation. SAMPLE POPULATION--100 mg of MPA or 4 mg of IPA was administered to 2 groups of 4 healthy sound radiographically normal female horses. PROCEDURE--Blood samples were collected at time 0 (before) and 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after administration of the designated steroid. Complete urine collection for measurement of designated steroid was ac...
Identification of metabolites of azaperone in horse urine. Two metabolites of the tranquilizer azaperone were extracted from alkalinized horse urine after treatment with beta-glucuronidase/sulfatase from limpets (Patella vulgata). The metabolites were identified by a combination of independent chemical synthesis and GC/MS and 1H NMR analysis. The metabolites were identified as 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1-piperazinyl]-1-butanol, designated as 5'-hydroxy-azaperol, and 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1-piperazinyl]-1-butanone, designated as 5'-hydroxyazaperone. A TLC screening test was developed for detecting both metabo...
Metabolic, hormonal, and hemodynamic changes during dopamine infusions in halothane anesthetized horses. Selected metabolites, hormones and cardiovascular variables were measured in halothane anesthetized horses during 1 hour of dopamine infusion at a rate of 5 micrograms/kg/min (low) and 10 micrograms/kg/min (high), and for 1 hour after infusion. Plasma cortisol increased twofold in the low-infusion group but did not change significantly in the high-infusion group. Plasma nonesterified fatty acids, blood glucose, blood lactate, and plasma insulin increased in the high-infusion group. There was little difference in heart rate, systolic, diastolic, and mean arterial blood pressure between the two ...
The pharmacokinetics or oral and intravenous allopurinol and intravenous oxypurinol in the horse. The pharmacokinetics of oral and intravenous allopurinol was studied in five horses and compared with intravenous oxypurinol. The plasma concentration vs. time curves, following intravenous administration of 5 mg/kg, were best described by the biexponential equations Cp = 106.58e(-25.14t) + 159.93e(-10.96t) for allopurinol and Cp = 321.09e(-9.72t) + 82.39e(-0.44t) for oxypurinol, with an elimination half-life (t1/2 beta) of 0.09 h and an area under the curve (AUC) of 19.8 mumol.h/L after intravenous administration, while the t1/2 beta and AUC of oxypurinol were 1.09 h and 231 mumol.h/L, respec...
Effects of exercise on plasma concentrations of caffeine and its metabolites in horses. The effects of exercise on the metabolism of caffeine (CA) were studied 3h after administration of the drug to race horses which then underwent exercise sets (1000-m gallop). Analysis was made of pharmacokinetics of CA, changes in its plasma concentrations, its metabolites, i.e., theophylline (TP), theobromine (TB) and paraxanthine (PX), and the molar concentration ratios of CA to these metabolites. After exercise, AUC and t1/2 tended to decrease, and the concentration of CA decreased, while the concentrations of TP and TB significantly increased. The TP/CA ratio and TB/CA ratio significantly ...
Simultaneous analysis of tiaramide metabolites in horse urine and plasma by solid-phase extraction and reversed-phase ion-pair liquid chromatography. A simple method for the simultaneous analysis of tiaramide (TRA) metabolites in the horse is described. The sample preparation method using a Bond-Elut PH cartridge and stepwise elution with ice-cold, 30% aqueous methanol followed by additional methanol is effective for recovering the metabolites with different properties. The extraction method gives good recoveries (greater than 80%) and reproducibility. Each metabolite is well separated by high-performance liquid chromatography using an octadecyl-type column of polymer-based packing with a solvent system of 20 mM phosphate buffer (pH 6.5)-ac...
Testosterone administration to mares: criteria for detection of testosterone abuse by analysis of metabolites in plasma and urine. A pharmacological dose of a long-acting testosterone ester, testosterone hexahydrobenzoate, was administered intramuscularly to two mares. The time course for some characteristic metabolites in blood and urine was then studied using an analytical method based on gas chromatography-mass spectrometry associated with stable isotope dilution. Among the plasma analytes, testosterone glucuronide was found to be the most adequate indicator for the monitoring of exogenous testosterone up to 2 weeks postadministration if a threshold value of 200 ng/L was applied. In urine, the simultaneous measurement ...
Preliminary study of the metabolism of 17 alpha-methyltestosterone in horses utilizing gas chromatography-mass spectrometric techniques. Little is known about the metabolism of 17 alpha-alkyl anabolic steroids in horses. In this study, the metabolism of 17 alpha-methyltestosterone is investigated by oral administration of a (1 + 1) mixture of the steroid and its deuteriated analogue. Both compounds were synthesized from dehydroisoandrosterone (DHA), using a Grignard reaction followed by an Oppenauer oxidation. Post-administration urine extracts were analysed by gas chromatography--mass spectrometry (GC-MS) using both electron impact (IE) and chemical ionization (CI). Interpretation of the data was facilitated by observation of ...
Screening of non-steroidal anti-inflammatory drugs, barbiturates and methyl xanthines in equine urine by gas chromatography-mass spectrometry. A gas chromatographic-mass spectrometric (GC-MS) screening procedure for 23 acidic drugs in equine urine is described. With the GC-MS method fifteen anti-inflammatory drugs, five barbiturates and three methyl xanthines can be detected with good sensitivity and selectivity. The method consists of alkaline hydrolysis, extraction with organic solvent using salting-out, clean-up extraction, methylation and screening with GC-MS in selected-ion monitoring mode. The limit of detection is 10 micrograms 1(-1) or lower, for most drugs.
Determination of xanthines by high-performance liquid chromatography and thin-layer chromatography in horse urine after ingestion of Guaraná powder. The seeds of Guaraná are rich in xanthines and are used for the preparation of guaraná powder which is very commonly given to horses as a 'tonic' in Brazil. In this paper, the xanthine content of guaraná powder was determined, in addition to its clearance time in horses. Thin-layer chromatography was used as a screening procedure and high-performance liquid chromatography was performed to quantify the drugs in both the powder and urine samples. The guaraná powder was found to contain 2.16, 1.10 and 36.78 mg g-1 of theobromine (TB), theophylline (TP) and caffeine (CF), respectively, and in ...
Disposition of human drug preparations in the horse. III. Orally administered alclofenac. Concentrations of the non-steroidal anti-inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi-compartmental model with two successive rate constants ka1 = 0.05 +/- 0.06 h-1 and ka2 = 0.06 +/- 0.01 h-1. Alclofenac half-lives t1/2 alpha and t1/2 beta were 1.0 +/- 0.8 h and 6.9 +/- 1.5 h, respectively. Maximal conc...
Effect of increasing work rate on metabolic responses of the donkey (Equus asinus). Oxygen consumption (VO2) and concentration of venous blood metabolites were measured in donkeys trained to run and to pull loads on a treadmill. VO2 in two donkeys running at maximal speed on a 9.8% slope was 110 +/- 2 ml.min-1.kg-1, approximately 22 times preexercise VO2. Average heart rate at maximal VO2 (VO2max) was 223 +/- 2 beats/min, five times the preexercise heart rate. Blood lactate increased 14-fold, and blood glucose did not change (P > 0.05). Animals running up a 4% incline and incremental draft loading of five donkeys walking on the level were also studied. The total energy cos...
Changes in concentrations of hormones, metabolites, and amino acids in plasma of adult horses relative to overnight feed deprivation followed by a pellet-hay meal fed at noon. Experiment 1 was conducted to characterize the concentrations of prolactin, growth hormone (GH), cortisol, insulin, glucagon, glucose, nonesterified fatty acids (NEFA), urea N, and 10 indispensable amino acids in the plasma of mares (n = 8) and stallions (n = 8) during the last 4 h of a 19-h period of feed deprivation and for 8 h after a noon meal. Experiment 2 was similar to Exp. 1 except that only stallions (n = 8) were used, and they were either fed (n = 4) or not fed (n = 4) at noon in a 2 x 2 Latin square design conducted over two sampling days 7 d apart. In Exp. 1, increases (P < .01)...
Concentration of ceftiofur metabolites in the plasma and lungs of horses following intramuscular treatment. Ceftiofur sodium, a broad spectrum cephalosporin antibiotic approved for veterinary use, is metabolized to desfuroylceftiofur which is conjugated to micro as well as macromolecules. Twelve horses, weighting 442-618 kg, were injected intramuscularly with a single dose of 2.2 mg ceftiofur/kg (1.0 mg/lb) body weight. Blood was collected at various intervals over 24 h after treatment. Three groups of four horses each were euthanized and lungs were collected at 1, 12, and 24 h after treatment. The concentration of desfuroylceftiofur and desfuroylceftiofur conjugates in the plasma and lungs was dete...
Investigation of the metabolism of azaperone in the horse. Urine samples collected from a horse after intramuscular administration of 40 mg of azaperone were extracted at pH 10 before and after acid hydrolysis. The extracts were concentrated and analysed by LC-MS-MS. Two N-dealkylated metabolites, N-despyridinylazaperol and N-despyridinylazaperone, and a low concentration of azaperone were detected in the unhydrolysed urine. Six metabolites; hydroxyazaperol, two hydroxyazaperones, azaperol, N-despyridinylazaperol and N-despyridinylazaperone were detected in the hydrolysed urine extracts. Using XAD-2 resin extraction, three glucuronide conjugated azape...
Urinary concentration of corticoids in normal horses and horses with hyperadrenocorticism. The urinary corticoid:creatinine (c:c) ratio was determined in eight horses with hyperadrenocorticism (HAC). The mean (+/- SD) urinary c:c ratio of the eight horses with HAC (29 +/- 14 x 10(-6)) was significantly (P < 0.05) greater than the ratio in seven control horses (11 +/- 4.3 x 10(-6)). The urinary concentration of corticoids in control horses (201 +/- 60.4 nmol litre-1) was significantly (P 0.05) between both groups. As both false negative and false positive cases were found, it is concluded that a measurement of the urinary c:c ratio in the horse should not be used as the sole test...
A liquid chromatographic method for the determination of fenoprofen in equine plasma and urine. A high performance liquid chromatographic method to measure plasma and urine fenoprofen levels in equine biofluids is described. Liquid-liquid extraction with diethylether was used to isolate the drug from plasma and urine. The accuracy and reproducibility of the method were within acceptable limits over the concentration range 0-10 micrograms/mL and 0-20 micrograms/mL respectively from plasma and urine. Detection limits were 0.05 microgram/mL (2 mL plasma) and 0.2 microgram/mL (0.5 mL urine). This procedure was applied to ascertain the pharmacokinetics of a 3 g dose of fenoprofen calcium in a...
Pharmacokinetics of phenylbutazone in neonatal foals. 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...
