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Topic:Pharmacokinetics
Pharmacokinetics in horses involves the study of how drugs are absorbed, distributed, metabolized, and excreted in equine species. This field of study provides insights into the time course of drug concentrations within the horse's body and helps in understanding the effects of various pharmaceuticals. Key parameters in equine pharmacokinetics include absorption rates, bioavailability, half-life, and clearance. These parameters can vary significantly due to factors such as age, breed, and health status of the horse. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacokinetic profiles of different drugs in horses, aiming to optimize dosing regimens and improve therapeutic outcomes in equine medicine.
Pharmacokinetic values of drugs frequently used in performance horses. Tables of values of pharmacokinetic variables (volume of distribution, total body clearance, and plasma elimination half-life) of drugs frequently administered to performance horses are accompanied by explanatory notes. Drugs described include the nonsteroidal anti-inflammatory drugs, corticosteroids, anabolic steroids, central nervous system-modifying drugs, respiratory system drugs, diuretics, local anesthetics, and antibacterial drugs.
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...
Pharmacokinetics of and serum thromboxane suppression by flunixin meglumine in healthy foals during the first month of life. 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. T...
Effects of sympathomimetic and sympatholytic drugs on exercise performance. This article has presented information on the importance of the sympathetic nervous system in the response to exercise. The authors have reviewed the very limited information on the effects of sympathomimetic and sympatholytic drugs on exercise performance in the horse. Most of these drugs are specifically prohibited under the rules of racing, and they have significant side effects that either decrease performance or make their use dangerous to both the horse and horse-man. Additionally, all of these drugs or their metabolites are readily detected by current drug testing protocols. Further inf...
Pharmacokinetics of metronidazole after rectal administration in horses. Five healthy adult mares and 1 gelding were given a single dose (15 mg/kg of body weight) of metronidazole per rectum. After manual evacuation of feces from the rectum, a suspension of crushed tablets and water (40 ml) was administered via a 28-F catheter advanced 30 cm into the rectum. Blood samples were obtained by jugular venipuncture, and metronidazole concentration was measured serially for the 14 hours after drug administration. Mean serum concentration of metronidazole peaked at 4.5 micrograms/ml, 0.83 hour after administration, and decreased to 0.38 microgram/ml, 14 hours after adminis...
Factors affecting drug withholding time estimates in horses. Although all the factors discussed in this article may have an effect on drug withholding time estimates, the factors that have the potential for the greatest effect or that have been found to cause positive tests in the past are 1. Dosage: Increasing the drug dosage will require a longer withholding time. 2. Dosing interval: Narrowing the dosing interval will require a longer withholding time. 3. Administration route: In general, oral administration results in lower peak plasma concentrations but may result in longer excretion in the urine and therefore longer withholding time. 4. Drug intera...
Effects of cocaine on incremental treadmill exercise in horses. Four mature horses were used to test the effects of two doses (50 and 200 mg) of intravenously administered cocaine on hemodynamics and selected indexes of performance [maximal heart rate (HRmax), treadmill velocity at HRmax, treadmill velocity needed to produce a blood lactate concentration of 4 mmol/l, maximal mixed venous blood lactate concentration, maximal treadmill work intensity, and test duration] measured during an incremental treadmill test. Both doses of cocaine increased HRmax approximately 7% (P < 0.05). Mean arterial pressure was 30 mmHg greater (P < 0.05) during the 4- to ...
Effects of single intravenously administered doses of omeprazole and ranitidine on intragastric pH and plasma gastrin concentration in nonfed ponies. We investigated the effects of a range of IV administered doses of omeprazole (0.125 to 2.0 mg/kg of body weight) on gastric pH (monitored by indwelling electrode) and plasma gastrin concentration, compared with those of IV administered ranitidine (1.0 mg/kg) in 4 Welsh mountain-type ponies. Pharmacokinetic variables of IV administered omeprazole also were examined. Episodes of high gastric pH in the basal state obscured the effect of acid suppression on intragastric pH; however, omeprazole induced dose-dependent increase in mean gastric pH (P < 0.01) during the 11 hours after its administr...
The intramuscular bioavailability of a phenylbutazone preparation in the horse. The plasma concentrations of phenylbutazone (PBZ) and its major metabolites, oxyphenbutazone (OPBZ) and gamma-OH-phenylbutazone (OHPBZ) were determined for up to 72 h in six horses, following intravenous (i.v.) and intramuscular (i.m.) administration of 4 g phenylbutazone, 20 ml Phenylarthrite Ventoquinol (Vetoquinol Spécialités Pharmaceutiques Vétérinaires, Magny-Vernois, 70200 Lure, France). After i.v. dosing the plasma disposition was best described by a two-compartment open model. The hydroxylated metabolites OPBZ and OHPBZ were present in detectable concentrations for 72 h and 48 h, r...
Determination of alclofenac in equine plasma and urine by high-performance liquid chromatography. A high-performance liquid chromatographic method to measure plasma and urinary alclofenac levels in equine biofluids is described. Isolation of the drug from plasma is achieved using liquid-liquid extraction with diethyl ether. Reversed-phase C18 solid phase extraction is used for the extraction of free and conjugated alclofenac from urine. The reproducibility and accuracy of the method were well within acceptable limits over the concentration ranges 0-10 and 0-20 micrograms/ml, respectively, for plasma and urine. Starting with 2 ml of plasma, a concentration of 0.1 microgram/ml could easily b...
Effects of concurrent administration of phenylbutazone and flunixin meglumine on pharmacokinetic variables and in vitro generation of thromboxane B2 in mares. 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 nonsteroid 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. Pharmaco...
Species scaling of propafenone disposition and concentration–time relationships among eight mammalian species. Usually, smaller mammals have higher clearances per unit body mass than do larger mammalian species. When clearance and other pharmacokinetic parameters are correlated with internal physiological processes, species tend to dispose of drugs at a similar pace. The first application of this concept is pharmacokinetic time, expressed with different units: Kallynochron, Apolysichron, Dienetichron, and Syndesichron. The present work describes pharmacokinetic time in these units from data obtained with propafenone in eight animal species: mouse, rat, rabbit, dog, sheep, human, cow, and horse. Additio...
Rapid high-performance liquid chromatographic method for the determination of ketamine and its metabolite dehydronorketamine in equine serum. A simple, rapid and sensitive high-performance liquid chromatographic procedure has been developed for the determination of ketamine and dehydronorketamine in equine serum. Sample preparation consisted of mixing equal volumes of serum and acetonitrile-phosphoric acid (85%)-water (20:2:78, v/v/v), followed by ultrafiltration through a 10,000 molecular mass cut-off filter. Separation of these two analytes in the ultrafiltrate was accomplished on a reversed-phase phenyl column eluted with methanol-acetonitrile-phosphate buffer solution. Ketamine and dehydronorketamine were detected by a variable ...
Kanamycin concentrations in synovial fluid after intramuscular administration in the horse. Six adult ponies were injected in the same intramuscular site with kanamycin sulphate (10 mg/kg). Two hours later, arthrocenteses of the right metacarpophalangeal, radio-carpal, intercarpal, tibio-tarsal and metatarsophalangeal joints were performed within 3 minutes. Arthrocenteses of the same joints on the left side were conducted 5 hours later. When expressed as a percentage of plasma drug concentration, differences in synovial fluid drug concentration between the joints sampled at 2 and 5 hours after injection were not detected.
The disposition of suxibuzone in the horse. A high performance liquid chromatographic method is described to determine the anti-inflammatory drug suxibuzone (SXB) and its major metabolites phenylbutazone (PBZ) and oxyphenbutazone (OPBZ) in equine plasma and urine. When suxibuzone (6 mg/kg) was administered intravenously (i.v.) or orally (p.o.) no parent drug was detected in plasma or in urine. The disposition of the metabolite PBZ (i.v.) could be described by a 2 compartment model with a beta half-life varying from 7.40 to 8.35 h. Due to severe side effects the use of i.v. suxibuzone should not be encouraged in the horse. PBZ and OPBZ w...
Disposition, bioavailability and clinical efficacy of orally administered acepromazine in the horse. The pharmacokinetics and pharmacological efficacy of orally (p.o.) administered acepromazine were studied and compared with the intravenous (i.v.) route of administration in a cross-over study using six horses. The oral kinetics of acepromazine can be described by a two-compartment open model with first-order absorption. The drug was rapidly absorbed after p.o. administration with a half-life of 0.84 h, tmax of 0.4 h and Cmax of 59 ng/ml. The elimination was slower after p.o. administration (half-life 6.04 h) than after i.v. injection (half-life 2.6 h). The bioavailability of the orally admini...
Evaluation of the effect of alfentanil on the minimum alveolar concentration of halothane in horses. The effect of 3 plasma concentrations of alfentanil on the minimum alveolar concentration (MAC) of halothane in horses was evaluated. Five healthy geldings were anesthetized on 3 occasions, using halothane in oxygen administered through a mask. After induction of anesthesia, horses were instrumented for measurement of blood pressure, airway pressure, and end-tidal halothane concentrations. Blood samples, for measurement of pH and blood gas tensions, were taken from the facial artery. Positive pressure ventilation was begun, maintaining PaCO2 at 49.1 +/- 3.3 mm of Hg and airway pressure at 20 +...
ELISA screening with GC-MS confirmation of the tranquilizer chlorprothixene administered in subtherapeutic doses to horses. A commercially available generic promazine ELISA kit is available which shows cross-reactivity for the tranquilizer chlorprothixene (CPT). The ELISA test readily detects the presence of CPT or its metabolites in equine urine for up to 24 h after the i.v. and i.m. administration of sub-therapeutic doses (4.5 mg) to three horses. Maximum concentrations (CPT equivalents) are obtained 2 h after i.v. dosing. No distinct concentration peak values are observed after i.m. administration. Following solid-phase extraction, confirmation of CPT and its metabolites by electron impact mass spectrometry afte...
Cardiovascular effects of thoracic compression in horses subjected to euthanasia. Six horses scheduled for euthanasia were instrumented for the measurement of blood flow by thermodilution, pulmonary arterial, right atrial and arterial blood pressures and collection of arterial blood for pH and blood gas analysis. The horses were anaesthetised with intravenous (iv) thiamylal sodium (10 mg/kg) and placed in right lateral recumbency. After euthanasia with an overdose of pentobarbitone sodium (100 mg/kg, iv) and loss of the electrocardiogram and arterial pulse pressure, thoracic compression at rates of 40, 60 and 80 compressions/min was instituted. Thoracic compression was acco...
Clinical pharmacokinetics of amikacin in hypoxic premature foals. The pharmacokinetics of amikacin, administered iv at 7 mg/kg, every 8 h, were evaluated over the first 48 h of hospitalisation in 7 critically ill hypoxic premature foals and compared with those in 8 full-term nonhypoxic critically ill neonatal foals. The pharmacokinetic data were used to calculate dosage schedules that would maintain the plasma amikacin concentrations in individual foals within a target range of > or = 15 micrograms/ml but < 30 micrograms/ml for peak values and < or = 3 micrograms/ml for trough values. The results indicated a statistically significant increase in the amikacin...
Pharmacokinetics of digoxin administered to horses with congestive heart failure. Nine horses with (naturally acquired) congestive heart failure were treated with 2.2 micrograms of digoxin/kg of body weight by the IV route, followed by 11 micrograms/kg administered orally every 12 hours thereafter. Furosemide was administered IV concurrently with IV administered digoxin every 12 hours. Serum concentration of digoxin was measured after the first (IV) and seventh (orally administered) dose. After IV administration, digoxin disposition was described by a 2-compartment model, with a rapid distribution phase (t1/2 alpha = 0.17 hour), followed by a slower elimination phase (beta ...
Clinical evaluation of romifidine/ketamine/halothane anaesthesia in horses. Romifidine, 100 micrograms/kg administered by intravenous injection, was evaluated as a premedicant to ketamine/halothane anaesthesia in 60 horses. Sedation developed within one to two minutes. In three cases mild staggering occurred within two minutes. Anaesthesia was induced after five minutes by the intravenous administration of ketamine (2 to 2.2 mg/kg). A mean time of 79 seconds elapsed before lateral recumbency was adopted. Fifty-four of the horses sank smoothly to the floor, with occasional steps sideways. Jaw tone, limb rigidity and mild muscle tremors often persisted for short periods...
Pharmacokinetics of single intravenous and single and multiple dose oral administration of rifampin in mares. The disposition of rifampin in six healthy mares after single intravenous (i.v.) and oral (p.o.) doses and after seven oral doses of 10 mg/kg administered twice a day was investigated using a high performance liquid chromatographic (HPLC) method. Pharmacokinetic variables for rifampin determined using the HPLC method were comparable to variables reported from earlier studies utilizing a microbiological assay. Desascetylrifampin, a major metabolite of the parent compound, could not be detected in the serum but was detected at low concentrations in urine. Mean trough concentrations of rifampin i...
Pharmacokinetics and metabolism of avermectins in livestock. The kinetics of avermectin disposition and metabolism in ruminant livestock and horses are reviewed with particular emphasis on the influence of route of administration and formulation on persistence of residues in tissues and excretion in faeces. Because information is not publicly available on other compounds in this class currently under development (e.g. moxidectin, doramectin), ivermectin only is considered. The biological half-life of ivermectin in plasma is similar in cattle and sheep but because of a larger volume of distribution, plasma clearance is more rapid in sheep. However, injec...
Treatment of respiratory infections in horses with ceftiofur sodium. Ceftiohr sodium was evaluated as a therapy for respiratory
infections in horses. This cephalosporin antimicrobial was
administered intramuscularly every 24 h and at a dose of 2.2
mglkg (1.0 mgllb) of body weight. The efficacy of ceftiofur
sodium was compared with that of a positive control drug,
ampicillin sodium (recommended dose of 6.6 mg/kg [3 mg/lb],
given every 12 h). Both treatments were continued for 48 h
after clinical symptoms were no longer evident (maximum of
10 days). Fifty-five (55) horses with naturally acquired
respiratory infections were included in the study; 28 were
...
A liquid chromatographic procedure for the analysis of yohimbine in equine serum and urine. A standardbred mare was dosed with 40 mg yohimbine intravenously. Serum and urine samples were collected and analyzed for yohimbine using solvent extraction and reversed-phase high-performance liquid chromatography (HPLC) with fluorescence detection. Maximum yohimbine concentrations of 45 and 18 ng/mL were observed in serum and urine samples, respectively. Elimination was rapid, with half-lives of approximately 20 and 53 min observed for serum and urine, respectively. The presence of yohimbine in these samples was confirmed by liquid chromatography/mass spectroscopy (LC/MS/MS).
Competitive inhibition of lipolytic enzymes. IX. A comparative study on the inhibition of pancreatic phospholipases A2 from different sources by (R)-2-acylamino phospholipid analogues. The inhibitory power (Z) of a number of (R)-1-alkyl-2-acylamino phospholipid analogues was determined for three mammalian phospholipases A2 from pig, ox and horse pancreas. All three enzymes display a clear preference for anionic (phosphoglycol) inhibitors over the zwitterionic (phosphocholine) derivatives; this effect is most pronounced for the bovine enzyme. Upon variation of the 1-alkyl chain length, the bovine and equine phospholipases, like the porcine enzyme in previous studies, show an optimum in Z for a six-carbon alkyl group. The introduction of a double bond in the 2-acylamino group ...
