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.
CLARKE EG.This research article explores the topic of doping racehorses, looking at the history of the practice, the reasons for it, various methods used, and the substances utilized. It also presents […]
BRAYE ET, HINSMAN EJ, RILEY WF.No horse receiving combined streptokinase, streptodornase, and human plasminogen alone in either 125,000-unit or 375,000-unit doses manifested any clinical reaction. Untoward reactions occurred in 2 horses receiving both the combined streptokinase, streptodornase, and human plasminogen (125,000 units), and chlortetracycline. The reaction was transitory and subsided without treatment.
Bardhi A, Barbarossa A, Joubert A, Gehring R, Lambertini C, Romagnoli N.Dried blood spot (DBS) sampling has emerged as a promising microsampling technique in biomedical and clinical research, offering advantages such as reduced invasiveness, minimal blood volume requirements, and enhanced analyte stability. Although well established in human medicine for neonatal screening and diagnostic applications, its potential in veterinary pharmacology remains underexplored. This study investigated the feasibility of using DBS samples to quantify anesthetic agents-ketamine and medetomidine in cats and lidocaine in horses-during routine surgical procedures at a veterinary tea...
Viljanto M, Cutler C, Habershon-Butcher J, Hincks P, Scarth J.The use of testosterone in racehorses is predominantly monitored using international urine and plasma concentration-based thresholds and complementary steroid ratios. To date, there has been no published pharmacokinetic study on transdermally applied testosterone products in horses and whether their use could result in adverse analytical findings. Therefore, quantitative analysis of testosterone and epitestosterone in urine and testosterone in plasma samples was performed following a pilot multi-dose transdermal Testogel administration (1 mg/kg once a day for 7 days on clipped skin) to one...
Baptiste KE, Kyvsgaard NC, Ahmed MO, Damborg P, Dowling PM.Rifampin is an enigma among antimicrobials. Blood and tissue compartment concentrations are a "moving target" along the treatment course due to the complex pharmacodynamic interactions within the body. Rifampin concomitant therapies are for the prevention and treatment of Rhodococcus equi infection in foals, for nearly 40 years. The necessity of rifampin concomitant therapies is based on beliefs that both antimicrobials (e.g., rifampin plus macrolide) penetrate into pulmonary abscesses and intracellular compartments above R. equi minimum inhibitory concentrations (MICs), as well as better ef...
So YM, Kwok WH, Tang CWY, Wong COL, Wan TSM, Ho ENM.This paper describes the studies of the in vitro biotransformation of nandrolone decanoate and its metabolic fate in equine plasma and urine after intramuscular administration to castrated thoroughbred horses. The in vitro metabolic study was performed using homogenised horse liver, and the more prominent in vitro biotransformation pathways were found to include hydrolysis, reduction, oxidation and sulfation, mainly resulting in seven Phase I metabolites and one Phase II metabolite. The administration study of nandrolone decanoate was carried out using three retired thoroughbred geldings, e...
Kuroda T, Minamijima Y, Niwa H, Mita H, Nomura M, Ohta M.A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the dosage regimens of trimethoprim/sulfamethoxazole for methicillin-resistant Staphylococcus aureus (MRSA) infections after intravenous (IV) and per os (PO) administration in horses. Methods: Trimethoprim/sulfamethoxazole plasma concentrations were measured in six horses after a single IV administration of 15 mg/kg (2.5 mg/kg trimethoprim and 12.5 mg/kg sulfamethoxazole) and PO administration of 30 mg/kg (5.0 mg/kg trimethoprim and 25.0 mg/kg sulfamethoxazole). The data were modeled using a nonlinear mixed-effects mode...
Bacon EK, Finno CJ, Donnelly CG, Haase B, Knych HK, Velie BD.Clinical assessments of equine sedation typically rely on subjective observations, the accuracy of which is paramount to the safety of equine veterinary procedures. Methods: To assess the degree in which subjective clinical sedative evaluations reflect pharmacokinetic measurements of equine drug metabolism, xylazine hydrochloride, an alpha-2 adrenoreceptor agonist, was administered to 36 horses of varying breed and age at a dosage of 0.5 mg/kg body weight. Subjective clinical parameters were scored at 5-, 15-, 30-, 45- and 60-minutes post xylazine administration and included responsiveness to ...
Wermer K, Korbacska-Kutasi O, Berkecz R, Csupor D, Ágh N, Sztojkov-Ivanov A, Cserhalmi D.Cannabidiol (CBD) has shown potential therapeutic benefits in veterinary medicine, but further investigations are needed to establish its pharmacokinetics and therapeutic dosing in horses and ponies. The present study aimed to investigate the pharmacokinetic properties of CBD in Connemara ponies following oral administration of CBD oil. Unassigned: Ten healthy ponies received a single oral dose of CBD oil at 2 mg/kg. Blood samples were collected before dosing and up to 16 days post-administration, with physical examinations conducted at baseline and at 8, 12, and 24 h post-dose. Addition...
Michanek P, Bröjer J, Lilliehöök I, Fjordbakk C, Erkas M, Löwgren M, Hedeland M, Bergquist J, Ekstrand C.Sodium-glucose co-transporter 2 inhibitors like canagliflozin (CFZ) have shown promise in preventing hyperinsulinemia-associated laminitis in horses, but data on pharmacokinetics, tolerability, and controlled studies are limited. This randomized, open-label, placebo-controlled, crossover study evaluated these aspects of CFZ treatment in eight healthy Standardbred mares. Each horse received single supratherapeutic oral doses of CFZ (1.8 mg/kg or 3.6 mg/kg) and placebo, with a two-week washout between treatments. A graded glucose infusion (GGI) was administered post-treatment to evaluate glu...
Barbosa LA, Maran AP, de Almeida MER, Guimarães EC, Bringel B, Douglas RH, Lima TFG, da Silva ESM.A longer endometrial exposure to estradiol before progesterone has been shown to be beneficial in cyclic and acyclic recipient mares. Therefore, the selection of an estradiol ester that promotes longer endometrial exposure to estradiol using a single administration would be advantageous when preparing acyclic mares as embryo recipients. This study investigated plasma estradiol profiles in acyclic mares after a single administration of 17-β estradiol (17-β), estradiol benzoate (EB) and estradiol cypionate (EC), and the correlation between plasma concentrations and endometrial edema. Fifteen n...
Morales CJ, Sykes BW, McKemie DS, Kass PH, Knych HK.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 ...
Calero IM, McKenzie EC, Johns JL.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...
Macias A, Delvescovo B, Donaldson SF, Divers TJ, Donnelly CG.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...
Honkavaara JM, Karikoski NP, Palvas L, Pypendop BH, Rinne VM, Raekallio MR.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...
Sullivan J, Blea J, McKemie DS, Kass PH, Knych HK.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...
Bish-Jones AR, Papich MG, Orsini JA.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...
Auvinen JRE, Kritchevsky JE, Reinhart JM, Gochenauer AE, Jannasch AS, Han-Hallett Y.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...
Loy J, Sornalingam K, Cawley A, Scrivener C, Keledjian J, Noble GK.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...
Minamijima Y, Kuroda T, Maeda Y, Narita S, Yamashita S, Yamada M.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...
Gray B, Lubbock K, Love C, Ryder E, Hudson S, Scarth J.The analytical approaches taken by laboratories to implement robust and efficient regulation of horseracing medication and doping control are complex and constantly evolving. Each laboratory's approach will be dictated by differences in regulatory, economic and scientific drivers specific to their local environment. However, in general, laboratories will all be undertaking developments and improvements to their screening strategies in order to meet new and emerging threats as well as provide improved service to their customers. In this paper, the published analytical advances in horseracing me...
Bailey CS, Beachler TM, Mochel JP, Wulf LW, Yaeger M, Kundu D, Withowski K, Papich MG.Despite their widespread clinical use, there is limited pharmacokinetic data for many equine intrauterine antimicrobials. This study aimed to measure the concentration of gentamicin and penicillin in the uterine fluid of mares following infusion of either a standard (PPGent) or long-acting (LA-PPGent) compounded formulation. We hypothesized that both formulations would result in therapeutic concentrations, with total concentrations sustained for longer using the long-acting formulation. Mares were administered 2400 mg of procaine penicillin and 200 mg of gentamicin via a single intrauterin...
Shimizu Y, Sugai-Bannai M, Tanabe H, Saito K, Ito H, Tokushige H, Kamiya K, Hirano-Kodaira M, Yamada M, Leung GN.Somapacitan is the second generation of recombinant human growth hormone (rhGH) medication that retains the pharmacological effects of rhGH but exhibits a longer duration of action due to its reversible albumin-binding in the body. In general, the use of all recombinant growth hormone (rGH) analogues is banned by the human and animal sports regulatory authorities due to their anabolic and lipolytic effects. However, little is known about the elimination kinetics and biological effects of the newly introduced long-acting rhGH, somapacitan, in horses. This paper describes the administration stud...
Hoh RL, Mama KR, Morales CJ, McKemie DS, Kass PH, Knych HK.To assess absorption after transdermal application of buprenorphine to different sites and assess behavioral, antinociceptive and adverse effects. It was hypothesized that the dose and site of transdermal buprenorphine administration would influence absorption, plasma drug concentrations, physiological, antinociceptive and behavioral effects in horses. Methods: Two-part study; prospective randomized balanced three-way crossover (study 1) and single-dose (study 2) experimental study. Methods: Six (study 1) and eight (study 2) horses, aged 3-14 years. Methods: In study 1, horses were administere...
Darby S, DeNotta S, Gomez DE.This report describes a case of ivermectin toxicosis in a 4-day-old thoroughbred colt successfully treated with intravenous lipid emulsion (ILE) without complications. This case supports the use of ILE as a safe and effective therapy for the management of lipophilic drug toxicosis in foals. Key clinical message: Ivermectin toxicosis, though rare in equine neonates, can occur following accidental overdose and induces severe neurologic signs. In this case, ILE administration resulted in rapid neurologic improvement and complete recovery without adverse effects, supporting its use as a safe and e...
Ekstrand C, Michanek P, Hernlund E, Gehring R, Spjut K, Salomonsson M.There has been a growing interest in the use of cannabinoids in horses in recent years. Several studies have reported on the pharmacokinetics of cannabidiol (CBD) in horses. However, cannabidiolic acid (CBDA) has received less attention, despite limited evidence suggesting clinically beneficial effects in other species. Horses were administered 3 mg/kg of CBD, 3 mg/kg of CBDA, and a placebo per os in a crossover design, with a one-week washout period between treatments. Plasma and urine samples were collected and analyzed using ultra high-performance liquid chromatography coupled to tandem...
Morgan JM, Gentille SR, Goyette FD, Lehman ML, Boss AL, Cassano JM, Knych HK, White SD.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...
Moore HL, Klabnik JL, Boothe DM, Cruz-Espindola C, Mita N, Thungrat K, Babu RJ, Lyman CC.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...
Kawashima M, Kuroda T, Minamijima Y, Yamazaki Y, Mita H, Nomura M, Ohta M.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....
Minamijima Y, Kuroda T, Okano A, Wakuno A, Yuasa R, Ishikawa Y, Nomura M, Kinoshita K, Yamada M.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...
Rocha IA, McPeek JL, Hulverson MA, Choi R, Orr K, Sponseller BT, Kennedy T, Ojo KK, Barrett LK, Ruby R, Janes J, Reed SM, Arnold SLM, Van Voorhis WC....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...
Kuroda T, Knych HK, Noble GK, Minamijima Y, Leung GN, Nomura M, Mizobe F, Ishikawa Y, Kusano K, Toutain PL.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...
