Omneity® Pellets
All-In-One Vitamin & Mineral Pellet
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.
Disposition of flunixin meglumine injectable preparation administered orally to healthy horses. An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.
Detection, quantification, metabolism, and behavioral effects of selegiline in horses. Selegiline ([R]-[-]N,alpha-dimethyl-N-2- propynylphenethylamine or l-deprenyl), an irreversible inhibitor of monoamine oxidase, is a classic antidyskinetic and antiparkinsonian agent widely used in human medicine both as monotherapy and as an adjunct to levodopa therapy. Selegiline is classified by the Association of Racing Commissioners International (ARCI) as a class 2 agent, and is considered to have high abuse potential in racing horses. A highly sensitive LC/MS/MS quantitative analytical method has been developed for selegiline and its potential metabolites amphetamine and methamphetamine...
Detection, quantification, and pharmacokinetics of furosemide and its effects on urinary specific gravity following IV administration to horses. Furosemide is a potent loop diuretic used for the prevention of exercise-induced pulmonary hemorrhage in horses. This drug may interfere with the detection of other substances by reducing urinary concentrations, so its use is strictly regulated. The regulation of furosemide in many racing jurisdictions is based on paired limits of urinary SG (100 ng/ml). To validate this regulatory mechanism, a liquid chromatography/mass spectrometry/mass spectrometry method employing a solid-phase extraction procedure and furosemide-d5 as an internal standard was developed. The method was used to determine th...
Survey of prokinetic use in horses with gastrointestinal injury. To report prokinetic strategies used to manage horses after gastrointestinal surgery. Methods: Electronic questionnaire. Methods: Diplomates of the American College of Veterinary Surgeons (ACVS) who perform equine intestinal surgery. Methods: A survey (21 questions) designed to determine use of prokinetic agents was sent electronically to 112 ACVS Diplomates known to perform equine intestinal surgery. Several clinical scenarios were also described to determine which, if any, prokinetic agent respondents would select. Results: Responses were obtained from 58 (52%) surgeons from 44 clinics. Sele...
Tissue distribution of clenbuterol in the horse. Plasma and tissue concentrations of clenbuterol (CLB) were determined following oral (p.o.) administration of 1.6 microg/kg twice daily (b.i.d.) for 2 weeks. Horses were administered the last dose on morning of day 15, killed at 0.25, 24, 48, and 72 h post-administration. At 0.25 h, the highest tissue concentrations of CLB were found in the liver (16.21 ng/g), lung (6.48 ng/g), left ventricle (4.99 ng/g), kidney (3.35 ng/g), bronchi (2.56 ng/g), right ventricle (2.08 ng/g), and eye fluids (1.09 ng/g) all of which were higher than that of plasma (1.10 ng/mL). The elimination half-lives (t(1/2k)...
Pharmacokinetics and disposition of clenbuterol in the horse. The pharmacokinetics of clenbuterol (CLB) following a single intravenous (i.v.) and oral (p.o.) administration twice daily for 7 days were investigated in thoroughbred horses. The plasma concentrations of CLB following i.v. administration declined mono-exponentially with a median elimination half-life (t(1/2k)) of 9.2 h, area under the time-concentration curve (AUC) of 12.4 ng.h/mL, and a zero-time concentration of 1.04 ng/mL. Volume of distribution (V(d)) was 1616.0 mL/kg and plasma clearance (Cl) was 120.0 mL/h/kg. The terminal portion of the plasma curve following multiple p.o. administrati...
The bioavailability and pharmacokinetics of glucosamine hydrochloride and chondroitin sulfate after oral and intravenous single dose administration in the horse. The purpose of this study was to determine if glucosamine (GL) hydrochloride (FCHG49) and low molecular weight (LMW) chondroitin sulfate (CS) (TRH122) are absorbed after oral administration to horses. The bioavailability of LMWCS was evaluated by quantifying the total disaccharides found in the plasma following chondroitinase ABC digestion. Methods: Two separate studies were conducted. In study 1, ten adult horses received the following four treatments in a randomized crossover fashion: (1) i.v. LMWCS (3 g of 8 kDa), (2) p.o. LMWCS (3 g of 8 kDa), (3) i.v. LMWCS (3 g of 16.9 kDa) and (4) p.o. ...
Pharmacokinetics of a high dose of amikacin administered at extended intervals to neonatal foals. To determine disposition kinetics of amikacin in neonatal foals administered high doses at extended intervals. Methods: 7 neonatal foals. Methods: Amikacin was administered (21 mg/kg, i.v., q 24 h) for 10 days. On days 1, 5, and 10, serial plasma samples were obtained for measurement of amikacin concentrations and determination of pharmacokinetics. Results: Mean +/- SD peak plasma concentrations of amikacin extrapolated to time 0 were 103.1 +/- 23.4, 102.9 +/- 9.8, and 120.7 +/- 17.9 microg/mL on days 1, 5, and 10, respectively. Plasma concentrations at 1 hour were 37.5 +/- 6.7, 32.9 +/- 2.6, ...
Influence of morphine sulfate on the halothane sparing effect of xylazine hydrochloride in horses. To quantitate the dose and time-related effects of morphine sulfate on the anesthetic sparing effect of xylazine hydrochloride in halothane-anesthetized horses and determine the associated plasma xylazine and morphine concentration-time profiles. Methods: 6 healthy adult horses. Methods: Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of halothane in O2 and characterize the anesthetic sparing effect (ie, decrease in MAC of halothane) by xylazine (0.5 mg/kg, i.v.) administration followed immediately by i.v. administration of saline (0.9% NaCI) solution, lo...
In vitro effects of oxytetracycline on matrix metalloproteinase-1 mRNA expression and on collagen gel contraction by cultured myofibroblasts obtained from the accessory ligament of foals. To determine the effects of oxytetracycline on matrix metalloproteinase-1 (MMP-1) mRNA expression and collagen gel contraction by equine myofibroblasts in an effort to explain the mechanistic basis for the pharmacologic treatment of flexural deformities in foals. Methods: Cultured myofibroblasts from the accessory ligament (distal check ligament) of 6 foals. Methods: Collagen gel scaffolds seeded with equine myofibroblasts were cultured in individual culture dishes containing complete media (Dulbecco's modified Eagle medium with 10% fetal bovine serum) and oxytetracycline (0, 12.5, 25, or 75 m...
Characterization of the pharmacokinetic and pharmacodynamic properties of the angiotensin-converting enzyme inhibitor, enalapril, in horses. The pharmacokinetics of enalapril (0.5 mg/kg i.v.) and the pharmacodynamics of enalapril (0.5 mg/kg PO) in 5 mares were investigated. After single i.v. dosing, concentrations of enalapril and enalaprilat, its active metabolite, were measured. Two weeks later, enalapril was administered by nasogastric tube. Potassium, creatinine, blood urea nitrogen (BUN), enalapril, and enalaprilat concentrations and angiotensin converting enzyme (ACE) activity were measured in serum. In addition, heart rate, blood pressure, digital venous blood gases, and lactate were measured. Two weeks later, enalapril was ...
Pharmacokinetics of recombinant hirudin in healthy horses. Recombinant (r)-hirudin is a specific inhibitor of thrombin that is independent of the activity of antithrombin. Objective: To evaluate pharmacokinetic properties and coagulatory changes of r-hirudin in healthy horses. Methods: Two clinically healthy horses received a single i.v. bolus of 0.4 mg/kg bwt r-hirudin and 6 clinically healthy horses received the same dose subcutaneously (subcut.) q. 12 h for 3 days. Coagulation times and r-hirudin plasma concentration were determined over 720 mins and 3 days after i.v. and subcut. administration, respectively. Results: In all horses, treatment with ...
Determination of xylazine and its metabolites by GC-MS in equine urine for doping analysis. Xylazine and its main metabolites were detected in equine urine after a single-dose intravenous administration of 0.98 and 1.01 mg/kg body weight xylazine, respectively, in two horses, in order to be used for equine doping control routine analysis. The urine levels of the parent drug and its metabolites were determined using gas chromatography-mass spectrometry (GC-MS). Xylazine is metabolised rapidly, down to a concentration level of about 1.0 microg/ml after 1-3h administration. Seven metabolites were identified in urine. 4-Hydroxy-xylazine, the major metabolite, could be traced for 25 h and...
Effect of nasogastric administration of sodium bicarbonate on carbon 13 isotopic enrichment of carbon dioxide in serum of horses. To determine the effect of administration of commercially available sodium bicarbonate (NaHCO3) on carbon 13 (13C) isotopic enrichment of carbon dioxide (CO2) in serum of horses. Methods: 7 healthy Thoroughbreds. Methods: Sodium bicarbonate (450 g) was administered via nasogastric intubation to horses. Horses had been fed a diet obtained from the same source and had access to water from the same source for 3 months before the study. Blood samples were collected immediately before and at 2, 4, 6, and 24 hours after administration of NaHCO3. The concentration of total CO2 in serum was measured b...
Effect of topical application of diclofenac liposomal suspension on experimentally induced subcutaneous inflammation in horses. To determine whether 1% diclofenac liposomal suspension (DLS) ointment would be absorbed transdermally and attenuate experimentally induced subcutaneous inflammation in horses. Methods: 7 healthy adult horses. Methods: Inflammation was produced by injecting 1% sterile carrageenan into subcutaneously implanted tissue cages 8 hours before (time -8) and at the time of application of test ointment. A crossover design was used. Horses received 1 of 2 treatments (topically administered control or DLS ointments) during 48 hours of carrageenan-induced subcutaneous inflammation. A single application of...
A GC-MS method for the determination of isoxsuprine in biological fluids of the horse utilizing electron impact ionization. Isoxsuprine is used to treat navicular disease and other lower-limb problems in the horse. Isoxsuprine is regulated as a class 4 compound by the Association of Racing Commissioners, International (ARCI) and, thus, requires regulatory monitoring. A gas chromatography-mass spectrometry method utilizing electron impact ionization was developed and validated for the quantitation of isoxsuprine in equine plasma or equine urine. The method utilized robotic solid-phase extraction and tri-methyl silyl ether products of derivatization. Products were bis-trimethylsilyl (TMS) isoxsuprine and tris-TMS rit...
Concentrations of gentamicin in serum and bronchial lavage fluid after once-daily aerosol administration to horses for seven days. To assess gentamicin concentrations in serum and bronchial lavage fluid (BLF) of horses during a 24-hour period after once-daily aerosol administration of gentamicin (GAER) for 7 days and the pattern and degree of bronchial tree inflammation associated with repeated GAER. Methods: 13 healthy adult horses (9 geldings and 4 mares). Methods: The treatment group comprised 8 horses, and 5 horses were untreated control animals. Gentamicin (20 mL of gentamicin [50 mg/mL]) was administered via aerosol once daily for 7 days. Samples of serum and BLF were obtained from all horses before GAER and 0.5, 4,...
Intramuscular dosing strategy for ampicillin sodium in horses, based on its distribution into tissue chambers before and after induction of inflammation. The Pharmacokinetics (PK) and distribution into tissue chamber fluid (TCF) of intramuscularly (i.m.) administered ampicillin sodium were examined in horses in order to design adequate dosing strategies. Concentration-time curves of ampicillin in plasma and TCF were determined in six horses following administration of 15 mg/kg ampicillin sodium, before and after the induction of local inflammation with 0.5% carrageenan. The calculated parameters were used to simulate various dosage-dosing interval combinations. Ampicillin was absorbed very rapidly following i.m. administration. Plasma concentra...
Pharmacokinetics and pharmacodynamic effects of amiodarone in plasma of ponies after single intravenous administration. Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electr...
Quantification and confirmation of flunixin in equine plasma by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. The method describes quantification and confirmation of flunixin in equine plasma by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC/Q-TOF/MS/MS). Samples were screened by enzyme-linked immunosorbent assay (ELISA) and only those samples presumptively declared positive were subjected to quantification and confirmation for the presence of flunixin by this method. The method is also readily adaptable to instrumental screening for the analyte. Flunixin was recovered from plasma by liquid-liquid extraction (LLE). The sample was diluted with 2 ml saturated phosphate buffer (pH ...
Antimicrobial therapy for gastrointestinal diseases. Antibiotics will always be needed in horses for many types of infections, but the adverse consequences also must be considered. For the conditions described in this article, there is justification for antibiotic therapy. The intestinal problems that antibiotics can induce are among the risks from their administration to horses. Disruption of the endogenous bacterial population, colitis, and diarrhea are the most common complications from antibiotic therapy.
Treatment and prevention of intestinal parasite-associated disease. Since 1917, only 11 new endoparasiticides have been developed for the horse, of which five chemical classes are in common use. The selection pressure of frequent administration of deworming doses for parasite control programs has been associated with the development of resistance of small strongyle parasites to the effects of benzimidazoles and pyrantel salts. Against the background of the inevitability of the occurrence of ivermectin/moxidectin resistance, responsible use of equine anthelmintics based on the clinical pharmacology of the compounds and the biology/epidemiology of intestinal par...
Clinical application of prokinetics. Intestinal stasis or ileus is a significant cause of mortality and morbidity in horses and has been attributed to a variety of causes, including loss of intrinsic or extrinsic electrical activity, incoordination of contractile activity from regional stimuli, and dissociation between electrical and mechanical activity. Proposed mechanisms include systemic shock, electrolyte disturbances, persistent luminal distention, ischemia, inflammation, peritonitis, endotoxemia, and anesthesia. Because the cause of ileus is likely multifactorial, a variety of pharmaceutics have been used to target specific...
Postnatal development of hepatic oxidative, hydrolytic and conjugative drug-metabolizing enzymes in female horses. Little is known about the effects of aging on the hepatic drug metabolizing capacity of horses despite the relatively long lifespan characterizing this species. A wide array of cytochrome P450 (CYP)-dependent monooxygenases, carboxylesterases and transferases were assayed in liver microsomes from 50 female horses in an age range between less than 1 year to over 12 years. Rather unexpectedly, both the CYP content and the activity of NADPH cytochrome c reductase rose as a function of age. Accordingly, a general increasing trend was recorded in the rate of the in vitro metabolism of the substrate...
Effects of injection of botulinum toxin type B into the external anal sphincter on anal pressure of horses. To determine effects on anal pressure of horses after local injection of the external anal sphincter with Clostridium botulinum toxin type B. Methods: 11 healthy adult horses. Methods: Peak and resting anal sphincter pressures were measured with a custom-made rectal probe that was connected to a pressure transducer. Pressures were measured before treatment and after injection with botulinum toxin type B (BTB) or saline (0.9% NaCl) solution. Dose titration with 500, 1,000, 1,500, and 2,500 U of BTB was completed. Physical changes, behavior, and anal pressure were recorded for each horse. Result...
In vitro inhibition of blood cholinesterase activities from horse, cow, and rat by tetrachlorvinphos. The organophosphorus insecticide tetrachlorvinphos (TCVP) is commonly used as a feed-through larvicide in many livestock species, including cattle and horses. Cholinesterase (ChE) activity in blood (generally plasma or whole blood) is often employed to assess organophosphorus insecticide intoxication in animals as well as humans. In many species, including horse and man, plasma contains predominantly butyrylcholinesterase whereas red blood cells in all species express exclusively acetylcholinesterase. To evalulate the comparative interaction of TCVP with blood ChEs in different species, we com...
Evaluation of iohexol clearance used to estimate glomerular filtration rate in clinically normal foals. To determine whether pharmacokinetic analysis of data derived from a single i.v. dose of iohexol could be used to predict creatinine clearance and evaluate simplified methods for predicting serum clearance of iohexol with data derived from 2 or 3 blood samples in clinically normal foals. Methods: 10 healthy foals. Methods: Serum disposition of iohexol and exogenous creatinine clearance was determined simultaneously in each foal (5 males and 5 females). A 3-compartment model of iohexol serum disposition was selected via standard methods. Iohexol clearance calculated from the model was compared ...
Furosemide continuous rate infusion in the horse: evaluation of enhanced efficacy and reduced side effects. Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically signific...
Bone gentamicin concentration after intra-articular injection or regional intravenous perfusion in the horse. To compare intra-articular (IA) and bone gentamicin concentrations achieved after intra-articular administration or regional intravenous perfusion (RIP). Methods: Experimental study. Methods: Twelve healthy adult horses. Methods: Horses were assigned to 2 treatment groups (n = 6/group): Group 1, 1 g gentamicin administered simultaneously in both left and right metacarpophalangeal joints and group 2, 1 g gentamicin administered simultaneously in both left and right lateral palmar veins. Serum, synovial fluid, and bone biopsy specimens were collected. Gentamicin concentrations were determined by...
