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.
Efficacy of intramuscular meperidine hydrochloride versus placebo in experimental foot lameness in horses. There are no peer reviewed, blinded controlled studies regarding the skeletal analgesic efficacy of intramuscularly administered meperidine in horses. Objective: Using an adjustable heart bar shoe model of equine foot pain, the objective of this study was to test the hypothesis that meperidine (pethidine) administered intramuscularly would prove more efficacious in alleviating lameness than a saline placebo. Methods: Crossover pharmacodynamic experiment. Methods: Eight healthy adult Thoroughbred horses randomly underwent weekly i.m. treatments 1 h after lameness induction: saline placebo (1â...
A comparison of two doses of omeprazole in the treatment of equine gastric ulcer syndrome: a blinded, randomised, clinical trial. Studies on omeprazole have reported that doses as low as 0.7 mg/kg bwt per os are potent suppressors of acid production. Yet, to date, no studies have compared treatment efficacy of different doses in clinical cases of equine gastric ulceration. Furthermore, no studies have been performed to compare the healing response of the squamous and glandular mucosa to acid suppression therapy. Objective: To compare: 1) the efficacy of 2 doses of omeprazole in the treatment of primary squamous and glandular gastric ulceration; and 2) the healing response of primary squamous and glandular gastric ulcer...
Pharmacokinetics and physiological effects of repeated oral administrations of tramadol in horses. This study evaluated the pharmacokinetics and physiological effects of tramadol during repeated oral administrations in horses. Nine adult healthy horses were administered tramadol at 5 and 10Â mg/kg orally every 12Â h for 5Â days in a randomized, crossover design with a 3-week washout between treatments. Plasma concentrations of tramadol, O- and N-desmethyltramadol (M1 and M2) were measured using Liquid-Chromatography-Mass Spectrometry at predetermined time points following each tramadol administration. Cardiovascular, respiratory and gastrointestinal physiological variables were monitored an...
Evaluation of the use of atropine sulfate, a combination of butylscopolammonium bromide and metamizole sodium, and flunixin meglumine to ameliorate clinical adverse effects of imidocarb dipropionate in horses. To evaluate the ability of atropine sulfate, butylscopolammonium bromide combined with metamizole sodium, and flunixin meglumine to ameliorate the clinical adverse effects of imidocarb dipropionate in horses. Methods: 28 horses with piroplasmosis. Methods: 28 horses were randomly assigned to 4 equal groups according to the pretreatment administered. Fifteen minutes before administration of 2.4 mg of imidocarb dipropionate/kg IM, horses in the first group were pretreated with 0.02 mg of atropine sulfate/kg IV, the second group with a combination of 0.2 mg of butylscopolammonium bromide/kg IV an...
Effects of dexmedetomidine and xylazine on cardiovascular function during total intravenous anaesthesia with midazolam and ketamine and recovery quality and duration in horses. To compare cardiovascular effects and recovery quality and duration of total intravenous anaesthesia (TIVA) with xylazine-ketamine-midazolam or dexmedetomidine-ketamine-midazolam. Methods: Prospective, randomized experimental cross-over trial. Methods: Eight adult warmblood horses. Methods: After sedation with acepromazine and either xylazine [0.5 mg kg(-1) , intravenously (IV)] or dexmedetomidine (3.5 μg kg(-1) IV) anaesthesia was induced with ketamine and midazolam and maintained with a constant rate infusion (CRI) of xylazine (1 mg kg(-1)  hour(-1) ) [XKM] or dexmedetomidine (7 μg...
Pharmacokinetics and safety of firocoxib after oral administration of repeated consecutive doses to neonatal foals. The purpose of this study was to determine the pharmacokinetics and safety profile of firocoxib in neonatal foals. Seven healthy foals were administered 0.1Â mg/kg firocoxib orally q24Â h for nine consecutive days, commencing at 36Â h of age. Blood was collected for firocoxib analysis using high-pressure liquid chromatography with fluorescence detection at 0 (dose #1 only), 0.25, 0.5, 1, 2, 4, 8, 16, and 24Â h after doses 1, 5, and 9. For all other doses (2, 3, 4, 6, 7, and 8), blood was collected immediately prior to the next dose (24 h trough). Elimination samples (36, 48, 72, 96, 120, and 1...
The influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion in the standing horse. This study investigated the influence of perfusate volume on antimicrobial concentration in synovial fluid following intravenous regional limb perfusion (IVRLP) and assessed the efficacy of low volume IVRLP. The front limbs of 9 horses were randomly assigned to 1 of 3 volume groups: 10 mL (Group 1), 30 mL (Group 2), or 60 mL (Group 3). A tourniquet was applied distal to the carpus and the limbs were perfused with 500 mg genta-micin diluted to the assigned volume via a catheter placed in the lateral palmar digital vein at the level of the proximal sesamoid bones. Synovial fluid samples were col...
Therapeutic plasma concentrations of epsilon aminocaproic acid and tranexamic acid in horses. Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans. Objective: We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in...
Pharmacokinetics and safety of silibinin in horses. To determine the oral bioavailability, single and multidose pharmacokinetics, and safety of silibinin, a milk thistle derivative, in healthy horses. Methods: 9 healthy horses. Methods: Horses were initially administered silibinin IV and silibinin phospholipid orally in feed and via nasogastric tube. Five horses then consumed increasing orally administered doses of silibinin phospholipid during 4 nonconsecutive weeks (0 mg/kg, 6.5 mg/kg, 13 mg/kg, and 26 mg/kg of body weight, twice daily for 7 days each week). Results: Bioavailability of orally administered silibinin phospholipid was 0.6% PO in...
A pilot phase II study of the efficacy and biosafety of doxorubicin chemotherapy in tumor-bearing equidae. The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses. Objective: To provide preliminary evidence of the efficacy of doxorubicin in tumor-bearing horses, explore drug pharmacokinetics profile, and estimate period of risk of exposure to drug residues. Methods: Twelve horses with 37 tumors. Methods: Treatment protocol included 6 treatments at 3-week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m(2) and 4 horses received 4 of 6 treatment cycles at 70 mg/m(2) . Clinical signs, tumor responses, and toxicoses...
Evaluation of efficacy of mineral oil, charcoal, and smectite in a rat model of equine cantharidin toxicosis. The efficacy of orally administered therapeutics for the treatment of cantharidin intoxication has not been evaluated in controlled studies. Objective: To develop a model of acute cantharidin intoxication in laboratory rats and to evaluate in this model the relative efficacy of 3 gastrointestinal therapies used to treat equine cantharidin toxicosis. Methods: Sixty-four male Sprague-Dawley rats. Methods: A blinded, randomized, controlled study was performed on rats surgically implanted with telemetry transmitters for evaluating heart rate, locomotor activity, and body temperature. Orogastric ad...
Disposition of firocoxib in equine plasma after an oral loading dose and a multiple dose regimen. The objective of this study was to determine if a single loading dose (LD), 3× the label dose of firocoxib oral paste, followed by nine maintenance doses at the current label dose achieves and maintains near steady state concentrations. Six healthy, adult mares were administered 0.3mg/kg of firocoxib on Day 0, and 0.1 mg/kg 24 h later on Day 1, and at 24 h intervals from Day 2 to Day 9, for a total of 10 doses. Blood samples were collected throughout the study. The mean firocoxib maximum plasma concentration and standard deviation was 199±97 ng/mL, 175±44 ng/mL and 183±50 ng/mL after the L...
Indenopyride derivative RTI-4587-073(l): a candidate for male contraception in stallions. The objective of this study was to determine whether an indenopyridine derivative RTI-4587-073(l) was a good candidate for male contraception in horses. We hypothesized that a single administration of RTI-4587-073(l) causes significant suppression of testicular function in stallions without affecting sexual behavior. Three Miniature horse stallions received a single dose of 12.5 mg/kg RTI-4587-073(l) orally (group "treated"), whereas three other Miniature horse stallions received placebo only (group "control"). Semen was collected and evaluated from all stallions twice a week for three baselin...
Plasma and pulmonary pharmacokinetics of desfuroylceftiofur acetamide after weekly administration of ceftiofur crystalline free acid to adult horses. Current labelling for the use of ceftiofur crystalline free acid (CCFA) in horses states that 2 i.m. doses must be administered 4 days apart to provide 10 days of therapeutic coverage. A 10 day treatment regimen is not sufficient for the long-term treatment of horses with severe lung consolidation or pleuropneumonia. There are currently no data to guide an appropriate dosing interval when a longer treatment regimen is warranted. Objective: To determine steady-state plasma and pulmonary epithelial lining fluid (PELF) concentrations of desfuroylceftiofur acetamide (DCA) after weekly i.m. adminis...
Clinical and pharmacokinetic effects of regional or general anaesthesia on intravenous regional limb perfusion with amikacin in horses. Antimicrobial i.v. regional limb perfusion (IV-RLP) is clinically performed on anaesthetised or sedated horses with or without regional anaesthesia. To date, no scientific data are available on the clinical and pharmacokinetic effects of these anaesthetic protocols on antimicrobial IV-RLP, which is believed to result in better tourniquet efficiency due to decreased movement. Objective: To determine the effects of regional or general anaesthesia on the clinical and synovial pharmacokinetic parameters of amikacin administered by IV-RLP to horses. Methods: Experimental crossover study. Methods: E...
Reduction in absorption of gallium maltolate in adult horses following oral administration with food: chemistry and pharmacokinetics. Gallium (Ga) is under study for the treatment of osteolytic disorders in equines. Previous studies indicate that oral gallium maltolate (GaM) would provide a higher bioavailability than oral Ga salts. However, oral administration to adult horses of 2 mg/kg of GaM, in the form of a solution mixed with food, did not lead to detectable Ga levels in plasma. Therefore, a study was performed to model the chemical behaviour of GaM in the digestive tract. The equilibrium formation constants for Ga(III) and maltol were calculated by means of UV–visible measurements and validated by 1H-NMR measurement...
Effects of clopidogrel on the platelet activation response in horses. To evaluate the platelet activation response before and after treatment with clopidogrel in horses. Methods: 12 healthy adult mares. Methods: In a masked study, horses (6/group) were randomly allocated to alternately receive placebo or clopidogrel via nasogastric tube at a loading dose of 4 mg/kg followed by 2 mg/kg every 24 hours. Blood samples were collected before and 72 hours after initiation of treatment for ADP- and collagen-induced light transmission aggregometry; determination of closure time in collagen-ADP cartridges; modified thrombelastography for comparison of maximal amplitudes g...
Quantitation of fluphenazine in equine serum following fluphenazine decanoate administration. Fluphenazine, a potent antipsychotic used to treat schizophrenia in humans, is used in racehorses as a performance-enhancing drug, and for that reason it has been banned by the Association of Racing Commissioners International. A liquid chromatography-tandem mass spectrometry method for detecting and quantitating fluphenazine in equine serum was developed and validated. The method was then employed to quantitate fluphenazine in serum samples collected from three study horses after intramuscular injection of fluphenazine decanoate. Stability testing showed that fluphenazine is stable in unextra...
Pharmacodynamic evaluation of 4 angiotensin-converting enzyme inhibitors in healthy adult horses. Angiotensin-converting enzyme (ACE) inhibitors are used in horses with cardiovascular disorders despite the paucity of available data regarding their efficacy. Objective: The degree of serum ACE inhibition varies considerably between drugs. Methods: Eight healthy adult horses. Methods: Randomized prospective study. Horses were fasted overnight prior to receiving one of 4 ACE inhibitors intragastrically, administered at one of 2 dosages, using a randomized Latin square design (benazepril: 0.5 and 0.25 mg/kg; ramipril: 0.3 and 0.1 mg/kg; quinapril: 0.25 and 0.125 mg/kg; perindopril: 0.1 and 0.05...
Detection and elimination profile of cathinone in equine after norephedrine (Propalin®) administration using a validated liquid chromatography-tandem mass spectrometry method. Cathinone is the principal psychostimulant present in the leaves of khat shrub, which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. Cathinone readily undergoes metabolism in vivo to form less potent cathine and norephedrine as the metabolites. However, the presence of cathine and norephedrine in biological fluids cannot be used as an indicator of cathinone administration. The metabolism of pseudoephedrine and ephedrine, commonly used in cold and allergy medications, also produces cathine and norephedrine, respectively, as the metabolites. Besides, cath...
A comparison of two morphine doses on the quality of recovery from general anaesthesia in horses. Previous studies indicated that perioperative morphine improves recovery quality after general anaesthesia in horses. This clinical trial investigated whether this effect was dose-dependant. Twenty-six horses anaesthetised for surgery were block-randomised to receive one of two intraoperative morphine treatments: Treatment M1 consisted of a constant rate infusion (CRI) of morphine at 0.1mg/kg/h, begun after a loading dose (LD) of 0.15 mg/kg. Treatment M2 was a CRI of 0.2mg/kg/h preceded by an LD of 0.3mg/kg. During recovery, times at the first attempt and at achieving sternal recumbency and st...
Pharmacokinetics and thrombolytic effects of the recombinant tissue-type plasminogen activator in horses. To test the efficacy of the recombinant tissue-type plasminogen activator (rt-PA) alteplase in horses, the thrombolytic effect was tested in in vitro generated equine thrombi. The extent of lysis was determined by measuring the decrease in thrombi weight over a period of 4 hours. In vivo pharmacokinetics of alteplase were determined in 6 healthy horses. A single dose (1 mg/kg) was applied via intravenous infusion over a period of 30 minutes Coagulation-related variables, blood count and clinical parameters were taken before the treatment and until 48 h after treatment. In addition, plasma rt-P...
A clinician’s guide to factors affecting withdrawal times for equine therapeutic medications. Equine forensic science can now detect concentrations down to 25 femtograms/mL (parts per quadrillion, ppq) or less in blood and urine. As such, horsemen are increasingly at risk of inadvertent 'positives' due to therapeutic medication 'overages' or trace identifications of dietary or environmental substances. Reviewed here are the factors which determine detection times and 'withdrawal times' for substances administered to horses. Withdrawal times are affected by many factors, including dose, formulation, route and frequency of administration, bioavailability, plasma half-life, sensitivity of...
Pharmacokinetics and pharmacodynamics of glycopyrrolate following a continuous-rate infusion in the horse. Glycopyrrolate (GLY) is an antimuscarinic agent that is used in humans and domestic animals primarily to reduce respiratory tract secretions during anesthesia and to reverse intra-operative bradycardia. Although GLY is used routinely in veterinary patients, there is limited information regarding its pharmacokinetic (PK) and pharmacodynamic (PD) properties in domestic animals, and an improved understanding of the plasma concentration-effect relationship in racehorses is warranted. To accomplish this, we characterize the pharmacokinetic-pharmacodynamic (PK-PD) actions of GLY during and after a 2...
Pharmacokinetics, pharmacodynamics and local tolerance at injection site of marbofloxacin administered by regional intravenous limb perfusion in standing horses. To evaluate pharmacokinetic-pharmacodynamic variables and local tolerance at injection-site of marbofloxacin administered via regional intravenous limb perfusion (RIVLP) in standing horses. Methods: Adult horses (n = 6). Methods: RIVLP were performed with rubber tourniquets applied to the forelimbs of standing sedated horses. Marbofloxacin (0.67 mg/kg) was randomly injected in 1 forelimb, with the contralateral limb serving as a control (0.9% NaCl solution). Samples of jugular blood and synovial fluid from the radiocarpal joint of the marbofloxacin-perfused limb were collected before and...
Disposition of methylprednisolone acetate in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses. Methylprednisolone acetate (MPA) is commonly administered to performance horses, and therefore, establishing appropriate withdrawal times prior to performance is critical. The objectives of this study were to describe the plasma pharmacokinetics of MPA and time-related urine and synovial fluid concentrations following intra-articular administration to sixteen racing fit adult Thoroughbred horses. Horses received a single intra-articular administration of MPA (100Â mg). Blood, urine, and synovial fluid samples were collected prior to and at various times up to 77Â days postdrug administration a...
The pharmacokinetics of methocarbamol and guaifenesin after single intravenous and multiple-dose oral administration of methocarbamol in the horse. A simple LC/MSMS method has been developed and fully validated to determine concentrations and characterize the concentration vs. time course of methocarbamol (MCBL) and guaifenesin (GGE) in plasma after a single intravenous dose and multiple oral dose administrations of MCBL to conditioned Thoroughbred horses. The plasma concentration-time profiles for MCBL after a single intravenous dose of 15 mg/kg of MCBL were best described by a three-compartment model. Mean extrapolated peak (C0 ) plasma concentrations were 23.2 (± 5.93) μg/mL. Terminal half-life, volume of distribution at steady-state...
Mutant prevention concentration and mutant selection window for 10 antimicrobial agents against Rhodococcus equi. The objectives of this study were to determine the mutant prevention concentration (MPC), time above the MPC and mutant selection window for 10 antimicrobial agents against Rhodococcus equi and to determine if the combination of a macrolide with rifampin would decrease emergence of resistant mutants. Antimicrobial agents investigated (erythromycin, clarithromycin, azithromycin, rifampin, amikacin, gentamicin, enrofloxacin, vancomycin, imipenem, and doxycycline) were selected based on in vitro activity and frequency of use in foals or people infected with R. equi. Each antimicrobial agent or co...
Efficacy of cyclo-oxygenase inhibition by two commercially available firocoxib products in horses. Two firocoxib preparations for oral use are approved for use in animals in many countries: a chewable canine tablet and an equine paste. In order to reduce costs, many veterinarians use the canine product in horses even though this is an off-label use of the preparation. Objective: To determine the relative efficacy of 2 commercially available firocoxib products to inhibit prostaglandin Eâ‚‚ (PGE2) synthesis after oral dosing in horses. Methods: A crossover design using 8 adult horses (n = 4 for each preparation during each treatment period). Body weight range 532-614 kg. Methods: Horses recei...