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.
Plasma and Urinary Elimination Profiles of Medetomidine Metabolites in Horses for the Purpose of Doping and Medication Control. Medetomidine, an α₂-adrenergic agonist, is widely used as a sedative in horses. While its pharmacological effects are established, limited data exist on elimination of its metabolites, 3'-hydroxy medetomidine (HMD) and 3'-carboxy medetomidine (CMD), which are of regulatory interest. HMD is currently targeted in plasma and urine under International Screening Limits (ISLs) established by the International Federation of Horseracing Authorities (IFHA). In this study, seven Thoroughbreds received 6.3 μg/kg of medetomidine intravenously. Blood and urine were collected for 96 h and analyzed b...
Pharmacokinetic analysis and steady-state predictions of different preparations of metronidazole administered per rectum in adult horses. Manipulation of forms of rectally administered metronidazole to improve bioavailability in horses has not been reported. Objective: Evaluate the pharmacokinetics of 3 rectal metronidazole preparations compared to nasogastric (NG) administration. Methods: Seven healthy horses. Methods: Phase 1A was a randomized, 3-way crossover, single-dose pharmacokinetic study, and Phases 1B and 2 were non-randomized, single-dose follow-up studies. Metronidazole (20 mg/kg) was administered NG and rectally in water (RW20), as a rectal gel (RG), and in dimethyl sulfoxide (DMSO). Metronidazole (80 mg/kg) was a...
Pharmacokinetics of Topical Administration of Altrenogest in Mares and Implications for Human Health. Altrenogest is a synthetic progestogen widely used in equine reproductive management. Adverse effects to altrenogest have been reported in people with cutaneous exposure reported as the highest exposure pathway. Despite these reports, there has been no quantitative research to determine the capacity for altrenogest to be absorbed through skin. This study aimed to determine if cutaneous application of oral altrenogest results in systemic absorption in mares and to evaluate the influence of application site. A randomized, two-period, two-treatment crossover study was undertaken in eight mares. M...
Ertapenem Pharmacokinetics in Equine Plasma and Synovial Fluid Following a Single Intravenous Dose. This study describes the pharmacokinetics of ertapenem, a carbapenem antimicrobial that has not been previously studied in equids. Administered as a 30 mg/kg intravenous bolus to six healthy horses, serial blood and synovial samples were obtained over 8 h after administration. Pharmacokinetic analysis of plasma and synovial fluid was performed. In plasma, the AUC was 353.10 h × μg/mL (CV = 49.02%), Vss 79.34 mL/kg (CV = 22.85%), CL 84.96 mL/h/kg (CV = 31.31%) and t1/2 2.03 h (CV = 15.32%). In synovial fluid, the AUC was 524.10 h × μg/mL (CV = 16.03...
Pharmacokinetics and Anti-Inflammatory Effects of Intramuscular Betamethasone in Exercised Thoroughbred Horses. The pharmacokinetics and pharmacodynamics of betamethasone following intra-articular administration to horses have been described; however, studies characterizing intramuscular administration are lacking. Twenty-four horses received an intramuscular dose of 12 mg betamethasone sodium phosphate/betamethasone acetate. Blood and urine were collected at post administration for up to 408 h. Concentrations of betamethasone were determined using LC-MS/MS and pharmacokinetic parameters determined using a Population PK three-compartment model. The duration of pharmacodynamic effects was assessed by...
Exposure to Subcutaneously Administered Butorphanol in Horses Pre-Treated With Detomidine or Detomidine-Vatinoxan. The aim of the study was to determine the exposure to subcutaneously administered butorphanol in horses pre-treated with intravenous (IV) detomidine, with or without vatinoxan, a peripherally selective alpha-adrenoceptor antagonist. Five healthy, adult horses received three IV treatments 7 days apart, in a randomized, cross-over design: detomidine 20 μg/kg (DET-B), detomidine 20 μg/kg with vatinoxan 200 μg/kg (DETVAT-B) and saline (S-B), all followed by 0.1 mg/kg of butorphanol administered subcutaneously 30 min later. Venous samples were collected between 10 and 270 min after...
Pharmacokinetics of Intragastric Ursodeoxycholic Acid and Its Impact on Bile Acid Profiles in Horses. Ursodeoxycholic acid (UDCA), a secondary bile acid (BA) with therapeutic applications, is standard therapy for cholestatic hepatopathies in humans. In recent years, its use has been increasingly explored in equine medicine for similar indications. Pharmacokinetic data for UDCA in horses are currently lacking. This study aimed to describe the pharmacokinetic parameters following a single intragastric administration of 15 mg/kg in nine healthy, fasted horses and to characterize the changes in their BA profiles. Plasma concentrations of UDCA were measured at specific time points using liquid ch...
Vonoprazan pharmacokinetics and effects on gastric pH following administration to fed and fasted horses. Current treatment options for equine gastric ulcer syndrome (EGUS), such as omeprazole-a proton pump inhibitor (PPI)-have notable limitations, including the need for administration on an empty stomach. Potassium-competitive acid blockers (P-CABs), such as vonoprazan, are a newer class of acid suppressants that offer several advantages over PPIs in humans and may provide similar benefits in horses. Objective: To describe the pharmacokinetics and effect of a single oral dose of vonoprazan on intragastric pH in horses. We hypothesised that vonoprazan would follow linear kinetics across the doses ...
Compounded oral doxycycline in late-term pregnant mares: pharmacokinetics, fetoplacental diffusion, and neonatal safety. Doxycycline is widely used in equine medicine, yet data on its pharmacokinetics and safety during late gestation are scarce. We investigated the pharmacokinetics, fetoplacental diffusion, and safety of compounded oral doxycycline in late-term pregnant mares. In the first experiment, six mares at 300 days of gestation received a single oral dose (10 mg/kg), and plasma concentrations were measured using LC-MS/MS. Pharmacokinetic analysis using non-compartmental and compartmental models showed rapid absorption, with a mean Cmax of about 6000 ng/mL reached within 0.8 h and a terminal half-life ...
In vitro inhibitory effects of gentamicin and ceftiofur against Trypanosoma evansi: Promising antibiotic alternatives for equine trypanosomosis in Thailand. infection (Surra) remains a major constraint to equine health and productivity in Thailand. The only available trypanocidal drug, diminazene aceturate (DA), has limited efficacy, poor blood-brain barrier penetration, and toxicity in horses. This study aimed to investigate the inhibitory effects of commonly used equine antibiotics, gentamicin (GMC), ceftiofur (CTF), and trimethoprim-sulfamethoxazole (TS), against (Thai strain isolated from dairy cattle number 953; TEDC 953) to identify potential therapeutic alternatives or adjuncts for equine trypanosomosis. Unassigned: An growth inhibition...
Time Attenuation Curves for Equine Intravenous Contrast Enhanced Skull CT Using the Medial Saphenous and Cephalic Veins. Intravenous (IV) contrast administration during computed tomography (CT) of the equine head is routinely performed to delineate the extent of disease and differentiate between vascular and nonvascular tissue. Current equine scan protocols are extrapolated from human and canine studies. There have been no prospective equine studies describing the optimal time to image the patient after administration of contrast or the optimal site of contrast administration. Therefore, the current postcontrast times to scan and sites of contrast administration may not be appropriate for use in horses. The obje...
Pharmacokinetics of a fipronil pour-on formulation and its efficacy against Dermacentor nitens (Acari: Ixodidae) in horses. The objective of this study was to standardize a stall-trial methodology for horses in order to evaluate the pharmacokinetics and efficacy of a 1 % fipronil pour-on formulation against Dermacentor nitens. Brazilian pony breed horses were housed in individual stalls within a covered barn and artificially infested with D. nitens larvae on alternate days from day -31 to -1 before treatment. The animals were treated on day 0 with a fipronil 1 % pour-on at a dose of 1 mg/Kg body weight. To determine the therapeutic efficacy, the number of engorged females naturally detached from control and t...
Pharmacokinetics and Safety of a Single Subcutaneous or Intramuscular Dose of Ketamine in Healthy Horses. Pharmacokinetics (PK) of intramuscular (IM) and subcutaneous (SC) ketamine in horses has not been described. This study aimed to evaluate the PK and safety of ketamine and its metabolites after a single SC or IM administration. In Phase 1, two horses received 0.5 or 1 mg/kg of ketamine via SC and IM routes. In Phase 2, eight horses received 0.5 mg/kg IM. Plasma or serum concentrations of ketamine and major metabolites were determined by a validated liquid chromatography-mass spectrometry method at baseline and selected intervals post-administration. Subcutaneous administration resulted in ...
Multi-pathogen lower respiratory tract infection including a fungal agent in a yearling mustang filly. This report describes the diagnosis and successful management of a yearling filly with Coombs-positive anemia, thrombocytopenia, and fungal pneumonia. Diagnostic procedures, including thoracic ultrasonography and radiography, respiratory pathogen PCR testing, and evaluation of tracheal wash and bronchoalveolar lavage samples established multi-pathogen lower respiratory tract infection including a fungal agent. Orally administered voriconazole was a key component of treatment in this case to successfully eliminate fungal infection, alongside therapies for managing hematologic disease. This case...
Characterization of intramuscular Isoflupredone acetate in horses: pharmacokinetics and effects on anti-inflammatory mediators and plasma electrolytes. Corticosteroids, such as isoflupredone, are effective anti-inflammatory medications and as such are commonly used to treat inflammation associated with training and injuries in performance horses. While the pharmacokinetics and pharmacodynamics of isoflupredone acetate (IPA) following intra-articular administration to horses has been well described, studies characterizing intramuscular (IM) administration are lacking. The objective of the current study was to describe the pharmacokinetics and anti-inflammatory effects of IPA following IM administration to horses. Twelve horses received a singl...
Oral administration of pimobendan in healthy horses results in low plasma concentrations. To describe the pharmacokinetics of a single dose of pimobendan (Vetmedin) in healthy adult horses and provide preliminary evidence of the absorption of 2 compounded pimobendan formulations. Unassigned: From August 2022 through November 2022, 6 healthy adult horses were administered a single dose of 0.5 mg/kg pimobendan orally. A subset of 2 horses was also administered pimobendan, compounded as an oil-based suspension and a capsule formulation. Plasma was collected at times 0, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, and 24 hours after administration. The plasma concentrations of pimobendan...
Metformin in the Horse: Pharmacokinetics and Detection Times Using Monte Carlo Simulations. The racehorse industry has strict regulations regarding the detection of prohibited substances in horses. Metformin, a diabetes medication, is a prohibited substance that has been reported in post-race blood and urine samples collected from racehorses. For further characterization of the disposition of metformin, 12 Thoroughbred horses were administered metformin orally and intravenously in a randomized, balanced, two-way crossover design. Serum and urine samples were collected, and drug concentrations determined via liquid chromatography-tandem mass spectrometry. The serum data were analyzed ...
Detection of Nandrolone Decanoate and Its Metabolites in Equine Hair After Intramuscular Administration. This paper describes the detection of nandrolone decanoate and its metabolites in mane hair collected from horses that have been treated with nandrolone decanoate (Deca-Durabolin). The intramuscular administration study of nandrolone decanoate in three Thoroughbred castrated horses (each received 800 mg weekly for 3 consecutive weeks) was previously conducted to investigate its metabolism and detection time in plasma and urine for doping control purposes. In this work, segmental analysis of the post-administration hair has revealed that (i) nandrolone decanoate and its metabolites, nandrolon...
Effects of Lidocaine Alone Versus Lidocaine-Dexmedetomidine Infusion on Pulmonary Gas Exchange and Respiratory Mechanics During Isoflurane Anesthesia in Horses. Dexmedetomidine improves pulmonary function in dogs and humans, but evidence in horses is scarce. This study evaluated dexmedetomidine infusion on oxygenation and respiratory mechanics in anesthetized horses. Twenty horses undergoing elective surgery were included in a prospective, non-randomized, observational study. Horses received either lidocaine alone (1.3 mg/kg over 15 min, then 3 mg/kg/hour; LIDO) or combined with dexmedetomidine (1.75 μg/kg over 15 min, then 1.75 μg/kg/hour; DL). Respiratory mechanics, gas exchange, and cardiovascular variables were recorded at baseline, post-loading...
Pharmacokinetics, pharmacodynamics, and local tolerance at injection site of penicillin and gentamicin administered by intravenous regional limb perfusion in standing horses: comparison between weightbearing and flexed limbs. Intravenous regional limb perfusion (IVRLP) of antibiotics is a therapeutic method used to treat distal limb infections in horses. The objectives of this study were to determine the pharmacokinetic parameters and tolerance of sodium benzylpenicillin (NaBP) administered via IVRLP; to compare the feasibility, tolerance, and efficacy of performing IVRLP on a flexed limb versus a weightbearing limb; and to predict the efficacy of IVRLP using gentamicin or NaBP. A prospective crossover study was conducted with six horses, each undergoing four phases of antibiotic infusion (gentamicin at 2.2 mg/kg ...
Metabolism, pharmacokinetics, and bioavailability of cannabigerol in horses following intravenous and oral administration with micellar and oil formulations. Cannabigerol (CBG) is a non-psychoactive cannabinoid with growing interest in veterinary medicine; however, its pharmacokinetic profile in horses remains unknown. Understanding its absorption, distribution, metabolism, and elimination is essential to optimizing dosing strategies and evaluating its potential for clinical use in equine patients. Unassigned: A prospective crossover study was conducted in eight healthy adult horses to assess the metabolism and the pharmacokinetics after intravenous (IV) administration at 1 mg/kg and oral administrations at 10 mg/kg with two formulations (mice...
A Meta-Analysis of International Flunixin Pharmacokinetics in Horses: Toward Regulatory Harmonization and Individualized Detection Times Using Bayesian Paradigm. Flunixin meglumine is widely used to manage pain and inflammation in horses, and its regulation requires robust pharmacokinetic analysis for harmonization. In this study, we conducted a meta-analysis of flunixin disposition using plasma and urine concentration data from 65 horses across four countries to robustly estimate pharmacokinetic parameters in setting screening limits (SLs) for controlling medications in horses. A population (POP) model was developed using nonlinear mixed-effects model analysis. The irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were det...
Bioanalytical Uncertainty Assessment of Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry Method for Caffeine and Lidocaine in Equine Antidoping: A Dual Perspective on Bottom-up and Top-Down Approaches. The quality of quantitative results in bioanalysis requires not only a validated analytical method but also a rigorous estimation of measurement uncertainty. This study examines the challenges associated with the implementation of two distinct approaches in equine anti-doping control for the assessment of uncertainty associated with an ultra-high-performance liquid chromatography-high resolution mass spectrometry quantitative method for caffeine and lidocaine in horse urine. The bottom-up approach, based on the ISO Guide to the Expression of Uncertainty in Measurement (ISO GUM), was compared t...
Pharmacokinetic analysis of bumped-kinase inhibitors in horses demonstrates their potential utility for prevention and treatment of equine protozoal myeloencephalitis. To determine the systemic and CNS distribution of bumped-kinase inhibitors (BKIs) in healthy horses, assess potential side effects, and identify a candidate compound for a clinical trial in equine protozoal myeloencephalitis (EPM) cases. Unassigned: 9 pharmacokinetic (PK) experiments were conducted from March 2021 through November 2024. Bumped-kinase inhibitors 1708, 1748, and 1841 were screened in Sarcocystis neurona growth assays and IV PKs, followed by investigation of a lead BKI compound by single-dose or multiday oral administration. Serial plasma collections were performed to assess syst...
Plasma and Urine Pharmacokinetics of Intravenous Pridinol in Thoroughbreds for Its Medication Control. We examined the pharmacokinetics of intravenous pridinol in six thoroughbred horses. Each horse received a single 20 mg dose of pridinol mesylate via the jugular vein, and plasma and urine samples were collected over 72 h. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to quantify pridinol concentrations in plasma and urine, allowing for the calculation of pharmacokinetic parameters. A three-compartment model best fit the plasma elimination data. Using the Toutain model, irrelevant plasma and urine concentrations were estimated to be 0.00284 and 0.000612 ng/mL, respec...
Equine Metabolism of Voxelotor and Its Impact on Hematological Indices: A Doping Control Perspective. Voxelotor, a therapeutic drug for sickle cell disease, has been reported to elevate serum erythropoietin and hemoglobin levels in healthy individuals. Because of its potential to alter blood parameters, the World Anti-Doping Agency (WADA) classified voxelotor under category M1 of the 2023 Prohibited List. Despite this classification, little is known about its metabolic behavior in either humans or animals. In this study, the metabolism of voxelotor was investigated in Thoroughbred horses after oral administration. Using liquid chromatography high-resolution mass spectrometry (LC-HRMS), 35 meta...
Pharmacokinetics of Remimazolam Versus Midazolam After Intravenous Administration to Horses. Remimazolam (RMZ) is a new short-half-life benzodiazepine used in humans. We compared the pharmacokinetics and sedative effects of RMZ with those of midazolam (MDZ) in Thoroughbred horses. Six Thoroughbreds received a single IV dose of RMZ 0.05 mg/kg or MDZ 0.05 mg/kg in a randomized crossover design. Blood samples were collected, and plasma RMZ and MDZ concentrations were measured by LC-MS/MS. Plasma concentrations were analyzed by using non-compartmental analysis and a nonlinear mixed effect model. The half-life of RMZ (0.77 ± 0.15 h) was significantly shorter than that of MDZ (3....
Pharmacokinetics and preliminary safety of single-dose oral fluralaner at 10 and 25 mg/kg in healthy horses revealed no adverse reactions. To determine the safety and pharmacokinetics of a single dose of the oral ectoparasiticide fluralaner at 10 and 25 mg/kg in healthy horses. Unassigned: 12 clinically healthy university-owned horses, 9 to 17 years of age, were administered a single oral dose of fluralaner at 10 or 25 mg/kg. Physical examinations, neurological examinations, plasma samples, hematology and biochemistry panels, and skin biopsies were collected throughout the 84-day trial period. Fluralaner concentrations were measured in plasma and skin by liquid chromatography-tandem mass spectrometry, and pharmacokinetics were ev...
Intravenous clomiphene citrate pharmacokinetics in healthy mares as a first step toward use in reproduction. To investigate the IV pharmacokinetic parameters of clomiphene citrate (CC), a selective estrogen receptor modulator, in mares. Unassigned: This was an experimental study to assess the pharmacokinetic parameters of CC in the mare. Eight mares received a single 2,000-mg dose of IV CC to identify plasma concentrations over 336 hours. Following this, 6 mares received a multidose regimen of IV CC (2,000 mg, q 24 h) for 5 days to identify trough plasma concentration each day. Unassigned: CC was well tolerated, demonstrated a short elimination half-life of 4.95 ± 1.10 hours and a mean residence tim...