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.
de Tonnerre DJ, Medina Torres CE, Stefanovski D, Robinson MA, Kemp KL, Bertin FR, van Eps AW.Sirolimus, a mechanistic target of rapamycin inhibitor, suppresses insulin production in other species and has therapeutic potential for hyperinsulinemia in horses. Objective: Determine the pharmacokinetics (PKs) of sirolimus and evaluate its effect on insulin dynamics in healthy and insulin dysregulation (ID) horses. Methods: Eight Standardbred geldings. Methods: A PK study was performed followed by a placebo-controlled, randomized, crossover study. Blood sirolimus concentrations were measured by liquid chromatography-mass-spectrometry. PK indices were estimated by fitting a 2-compartment mod...
Mercer MA, Davis JL, McKenzie HC, Messenger KM, Schaefer E, Council-Troche RM, Werre SR.Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic. Objective: To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia. Methods: Eight university owned research horses with experimentally induced endotoxemia. Methods: Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1 mg/kg, PO; FLU), and placebo (PO; PLAC) 2 hours after administration of LPS. Plasma ...
Castro-Cuellar G, Cremer J, Queiroz-Williams P, Knych HK, Leise BS.The objective of this study was to describe the pharmacokinetics of intra-articular (IA) administered buprenorphine in horses with lipopolysaccharide (LPS)-induced synovitis. Radiocarpal synovitis was induced in six healthy adult horses with the IA injection of LPS (0.5 ng/joint) on two occasions in a randomized cross-over design. Treatments (IA buprenorphine (IAB) at 5 μg/kg plus intravenous saline; and intravenous buprenorphine (IVB) at 5 μg/kg plus IA saline) were administered 4 h following LPS injection. Concentrations of buprenorphine were assessed in plasma and synovial fluid (SF) ...
Ryan CA, McNeal CD, Credille BC.Equine practitioners require recommendations that support antimicrobial stewardship and avoid generating resistance to medically important antibiotics. This review examines current inadequacies in antimicrobial stewardship standards within the veterinary community, related to antimicrobial categorisation and prescribing practices. Resistance to cephalosporin antibiotics in horses is also described. Properties of cephalosporin antibiotics are outlined and equine-specific studies of ceftiofur, a third-generation cephalosporin antibiotic with medical importance, are detailed. Readers are provided...
Foreman-Hesterberg CR, Foreman JH.Muscle damage can result in leakage of intracellular enzymes such as creatine kinase (CK) and aspartate transaminase (AST) into plasma. There are no controlled documentations of the effects of intramuscular antibiotic drug administration on plasma CK and AST activities in horses. The objective of this experiment was to test the hypothesis that 5 days of intramuscular procaine penicillin G injection in normal horses would result in increased plasma activities of CK and AST. Nine healthy adult horses were sampled for 7 days preceding, 5 days during, and 32 days following procaine penicillin G (2...
Sánchez de Medina A, Serrano-Rodríguez JM, Díez de Castro E, García-Valverde MT, Saitua A, Becero M, Muñoz A, Ferreiro-Vera C....Intravenous pharmacokinetics and oral bioavailability of cannabidiol (CBD) with different formulations have not been investigated in horses and may represent a starting point for clinical studies. Objective: To describe pharmacokinetics after intravenous and oral administrations with oil and micellar formulations and simulate different treatments. Methods: Single intravenous experiment and two-way randomised oral experiments, Latin-square design. Methods: Eight healthy horses received intravenous CBD at 1.00 mg/kg dose, oral CBD in sesame oil and in micellar formulation, both at 10.00 mg/k...
Fadel C, Giorgi M.According to in vitro and in vivo investigations, firocoxib (FX), a second-generation coxib, is a highly selective COX-2 inhibitor in horses. With a COX-1/COX-2 IC50 ratio of 643 in horses, FX spares the COX-1 inhibitory effects. It is approved for the treatment of musculoskeletal problems and lameness in horses and dogs with osteoarthritis (OA). For the treatment of OA in horses, both an injectable formulation for IV administration at a dose of 0.09 mg/kg for five days and an oral paste formulation at a dose of 0.1 mg/kg for 14 days are licensed. Numerous analytical methods were reported in...
Song Y, Day CM, Afinjuomo F, Tan JE, Page SW, Garg S.While the global market for veterinary products has been expanding rapidly, there is still a lack of specialist knowledge of equine pharmaceutics. In many cases, the basic structure of the gastrointestinal tract (GIT) and integumentary system of the horse shares similarities with those of humans. Generally, the dosage form developed for humans can be repurposed to deliver equine medications; however, due to physiological variation, the therapeutic outcomes can be unpredictable. This is an area that requires more research, as there is a clear deficiency in literature precedence on drug delivery...
Hammad A, Gadallah S, Misk T, Sharshar A, Thabet N, Mourad A.This study describes the selected pharmacodynamics and pharmacokinetics of nalbuphine (NAL) in xylazine (XYL)‑sedated horses. Five adult healthy horses were randomly received 2 treatments at a 1‑week interval; XYL treatment (0.55 mg/kg IV) and XYL/NAL treatment (XYL, 0.55 mg/kg IV; NAL, 0.3 mg/kg IV). The measured pharmacodynamic variables were sedative and analgesic effects and the effect on ataxia and some physiological parameters. for the pharmacokinetics of NAL, its plasma concentrations were measured using HPLC and a 2‑compartment analysis was performed. Greater and prolonged sedati...
Xue C, Davis J, Berghaus LJ, Hanafi A, Vaughn SA, Hart KA.Donkeys with clinical signs of pituitary pars intermedia dysfunction are treated with oral pergolide mesylate despite the lack of species-specific pharmacokinetic data. Objective: To evaluate the pharmacokinetics of intragastric and oral pergolide mesylate in healthy donkeys (Equus asinus). Methods: Pharmacokinetic study. Methods: Six healthy donkeys were administered pergolide mesylate (Prascend®) at 2 μg/kg bodyweight (bwt) intragastrically once, then once daily per os (PO) for 5 days. Blood samples were collected at 0, 10, 20, 30 and 45 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and ...
Gold JR, Grubb T, Court M, Villarino NF.Acetaminophen is a common analgesic and antipyretic drug used in human medicine and might be an alternative to nonsteroidal anti-inflammatory drugs for treating pain and pyrexia in foals. The pharmacokinetics and safety of differing doses of acetaminophen have not been investigated in foals. Objective: To determine the plasma pharmacokinetics and any changes in haematology and biochemistry profiles following oral administration of single doses of acetaminophen at 10, 20, and 40 mg/kg to foals. Methods: Randomised cross-over pharmacokinetic study. Methods: Six Quarter Horse (two colts and fou...
Marzok M, Almubarak AI, Kandeel M, El-Khodery S.Epidural analgesia using the alpha-2 agonist detomidine (DE), alone or in combination with lidocaine (LD), is frequently employed for standing surgical procedures in horses, but its use has not been evaluated in donkeys. Methods: In a randomised controlled prospective trial, 24 healthy adult donkeys were assigned to four groups (n = 6), each receiving 40 μg/kg of DE, 0.22 mg/kg of LD, combined DE and LD (DELD) or 0.9% sterile normal saline epidurally. After epidural injection of each treatment, the onset, degree and duration of sedation and anatomical extension of anti-nociception were obse...
Maney JK, Dzikiti BT, Escobar A, Knych HK, Bennett RC.Morphine is the prototypical μ-opioid receptor agonist used to provide analgesia in veterinary species. Its effects are well-described in horses but not donkeys. Objective: To determine the antinociceptive effects of two doses of morphine in donkeys. To describe preliminary pharmacokinetic parameters of morphine in donkeys. Methods: In vivo experiment. Methods: Eight adult castrated male donkeys were given intravenous (IV) 0.9% saline, morphine 0.1 mg/kg bwt (LDM), or morphine 0.5 mg/kg bwt (HDM) in a randomised order with a minimum 1-week washout period. Mechanical nociceptive thresholds (...
Sanches GL, Ribeiro LMF, Motta AP, Petrucci LBDV, Gobbi FP, Quirino CR, Di Filippo PA.This study aimed to compare the antinociceptive effects of tramadol 5% and lidocaine 2% on mental nerve block in horses of the Brazilian Pony breed. Eight adult non-pregnant mares were used in this study. The ponies were tranquilized with acepromazine (5 µg kg, IV), and the infiltration of the mental foramen was performed in Treatment 1- tramadol 5% (T, 150 mg) or Treatment 2- lidocaine 2% (L, 60 mg), both at a total dose of 3 ml in each foramen. Heart rate (HR), respiratory rate (RR), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), rectal te...
Peraza J, Hector RC, Lee S, Terhaar HM, Knych HK, Wotman KL.Acetaminophen (paracetamol) is increasingly used to treat painful conditions in horses but its ocular penetration has not been studied. Objective: To determine whether orally administered acetaminophen penetrates the aqueous humour of the normal equine eye and report an aqueous humour:serum acetaminophen concentration ratio in horses. Methods: In vivo experiment. Methods: Six privately owned horses with normal ophthalmic examinations weighing 568 ± 65 kg (mean ± standard deviation) and aged 11 ± 4 years were given 20 mg/kg acetaminophen orally every 12 h for a total of s...
Knych HK, Weiner D, Harrison L, McKemie DS.Intra-articular corticosteroids, such as isoflupredone acetate, are commonly used in the treatment of joint inflammation, especially in performance horses. Following administration in a non-inflamed joints blood concentrations of isoflupredone were low and detectable for only a short period of time post-administration compared to synovial fluid concentrations. For some drugs, inflammation can affect pharmacokinetics, therefore, the goal of the current study was to describe the pharmacokinetics of isoflupredone acetate following intra-articular administration using a model of acute synovitis. S...
Knych HK, Mama K, Oakleaf M, Harrison LM, McKemie DS, Kass PH.The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses. Methods: 12 research horses. Methods: Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration...
DrugCentral monitors new drug approvals and standardizes drug information. The current update contains 285 drugs (131 for human use). New additions include: (i) the integration of veterinary drugs (154 for animal use only), (ii) the addition of 66 documented off-label uses and iii) the identification of adverse drug events from pharmacovigilance data for pediatric and geriatric patients. Additional enhancements include chemical substructure searching using SMILES and 'Target Cards' based on UniProt accession codes. Statistics of interests include the following: (i) 60% of the covered drugs are...
Sandbaumhüter FA, Aerts JT, Theurillat R, Andrén PE, Thormann W, Jansson ET.The chiral drug ketamine has long-lasting antidepressant effects with a fast onset and is also suitable to treat patients with therapy-resistant depression. The metabolite hydroxynorketamine (HNK) plays an important role in the antidepressant mechanism of action. Hydroxylation at the cyclohexanone ring occurs at positions 4, 5, and 6 and produces a total of 12 stereoisomers. Among those, the four 6HNK stereoisomers have the strongest antidepressant effects. Capillary electrophoresis with highly sulfated γ-cyclodextrin (CD) as a chiral selector in combination with mass spectrometry (MS) was us...
Pusterla N, Vaala W, Bain FT, Chappell DE, Craig B, Schneider C, Barnett DC, Gaughan E, Papich MG.Equine protozoal myeloencephalitis (EPM) has remained a devastating neurological disease of the Americas, especially in young performance horses. Prophylactic treatment strategies with diclazuril have shown to reduce seroprevalence and titer levels to Sarcocystis neurona in healthy horses continuously exposed to the apicomplexan parasite. The goal of this study was to determine if the FDA-labeled dose of 1 mg/kg of 1.56% diclazuril (Protazil) given once weekly to healthy adult horses would achieve steady-state concentrations in plasma known to be inhibitory to S. neurona in cell culture. Five ...
Dobler D, Gerber M, Schmidts TM, Runkel F, Schlupp P.Human nail diseases, mostly caused by fungal infections, are common and difficult to treat. The development and testing of new drugs and drug delivery systems for the treatment of nail diseases is often limited by the lack of human nail material for permeation studies. Animal material is frequently used, but there are only few comparative data on the human nail plate, and there is neither a standardized test design nor a nail bed analogue to study drug uptake into the nail. In this study, a new permeation device was developed for permeation studies, and the permeation behavior of three model s...
Philip M, Karakka Kal AK, Subhahar MB, Karatt TK, Mathew B, Perwad Z, Graiban FM, Caveney MR, Sayed R, Kadry AM.According to previous research, aminorex is the major metabolite of levamisole; however, in the screening of levamisole-positive racehorse urine and plasma samples, aminorex could only be detected in trace amounts or not at all. In forensic laboratories, hydroxy levamisole and its phase II conjugates make it easier to confirm levamisole misuse and to differentiate between the abuse of levamisole and aminorex. This study aimed to identify the major levamisole metabolites that can be detected along with the parent drug. Methods: The study describes levamisole and its metabolites in thoroughbred ...
Adler DMT, Jørgensen E, Cornett C.To determine the synovial fluid (SF) concentrations of lidocaine and mepivacaine after intra-articular injection with clinically relevant doses to the distal interphalangeal (DIP), metacarpophalangeal (MCP), middle carpal (MC), and tarsocrural (TC) joint at two different time points after injection in order to be able to compare concentrations with previously established concentrations associated with cytotoxicity and antimicrobial activity. Unassigned: In the first of two experiments, 20 joints (5 MC, 5 MCP, 10 DIP joints) of five horses under general anesthesia were injected with clinically ...
Wilson KE, Bogers SH, Council-Troche RM, Davis JL.To determine the effects of general anesthesia on the safety and efficacy of co-administered potassium penicillin G (PEN) and gentamicin (GENT) in horses. Methods: Nonrandomized crossover. Methods: Six adult, Thoroughbred horses. Methods: Horses were administered PEN (22 000 IU/kg IV) and GENT (6.6 mg/kg IV). Plasma samples were collected over a 6 h period and synovial fluid was collected at 30 min and 6 h respectively. Drug administration and sample collection protocols were repeated after at least a 48 hour washout period and induction of anesthesia using xylazine/ketamine and main...
Kuroda T, Minamijima Y, Mita H, Tamura N, Fukuda K, Kuwano A, Toutain PL, Sato F.A pharmacokinetics/pharmacodynamics (PK/PD) approach was used to determine the best empirical dosage regimen of cefazolin (CEZ) after intramuscular (IM) administration of CEZ in horses. Seven horses received a single IM or intravenous (IV) administration of CEZ of 5 mg/kg bodyweight (BW) according to a crossover design. CEZ plasma concentrations were measured using LC-MS/MS. The plasma concentrations in these seven horses and those of six other horses obtained in a previous study with an IV CEZ dose of 10 mg/kg were modelled simultaneously using NonLinear Mixed-Effect modelling followed by M...
Brewer K, Machin J, Maylin G, Fenger C, Morales-Briceño A, Tobin T.Gabapentin, 1-(Aminomethyl)cyclohexaneacetic acid, MW 171.240, is a frequently prescribed high dose human medication that is also used recreationally. Gabapentin is orally absorbed; the dose can be 3,000 mg/day and it is excreted essentially unchanged in urine. Gabapentin is stable in the environment and routinely detected in urban wastewater. Gabapentin randomly transfers from humans to racing horses and is at times detected at pharmacologically ineffective / trace level concentrations in equine plasma and urine. In Ohio racing between January 2019 and July 2020,18 Gabapentin identifications...
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Sato F, Kuroda T, Yamada M, Leung GN.In drug metabolism studies in horses, non-targeted analysis by means of liquid chromatography coupled with high-resolution mass spectrometry with data-dependent acquisition (DDA) has recently become increasingly popular for rapid identification of potential biomarkers in post-administration biological samples. However, the most commonly encountered problem is the presence of highly abundant interfering components that co-elute with the target substances, especially if the concentrations of these substances are relatively low. In this study, we evaluated the possibility of expanding DDA coverag...
Ebner L, O O, Simon B, Lizarraga I, Smith J, Cox S.The pharmacokinetics of butorphanol after intravenous (IVB) and intramuscular (IMB) administration in donkeys were determined in this preliminary study. Healthy male gelded donkeys ( = 5), aged 6-12 years old, were administered 0.1 mg/kg butorphanol IV or IM in a randomized, crossover design. Blood samples were obtained at predetermined intervals for 24 h (IVB) and 48 h (IMB) after administration. Plasma butorphanol concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters were calculated. Following IVB administration, mean (± SE) apparent volume ...
Carlson A, Johnson PJ, Lei Z, Keegan KG.Soluble epoxide hydrolase (sEH) inhibitors are novel anti-inflammatory and analgesic agents that could improve pain management in horses. The objective of the present study was to evaluate the anti-nociceptive effect of a single-dose intravenous administration of the sEH inhibitor trans-4-{4-[3-(4-trifluro-methoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB) using an adjustable heart bar shoe (a-HBS) model of lameness. We hypothesized that t-TUCB would improve objective and subjective lameness measures compared to the control. Methods: Reversible lameness was induced in 8 horses for 24...
Kuroda T, Minamijima Y, Niwa H, Mita H, Tamura N, Fukuda K, Kuwano A, Sato F.Cephalothin (CET) concentrations in body fluids (plasma, synovial fluid, pleural fluid, peritoneal fluid, and aqueous humor) and tissue samples (bone, lung, jejunum, hoof, and subcutaneous tissue) were investigated to consider the treatment of infectious diseases in horses. CET 22 mg/kg body weight was intravenously administered to 12 horses. Samples were collected from four different horses at 1, 3, and 5 hr after administration. The CET concentration in body fluids other than aqueous humor was maintained above the MIC90 values of Streptococcus zooepidemicus and Staphylococcus aureus until 5 ...
Pérez R, Cabezas I, Sutra JF, Galtier P, Alvinerie M.A study was undertaken to evaluate and compare faecal excretion of moxidectin and ivermectin in horses after oral administration of commercially available preparations. Ten clinically healthy adult horses, weighing 390-446 kg body weight (b.w.), were allocated to two experimental groups. Group I was treated with an oral gel formulation of moxidectin at the manufacturer's recommended therapeutic dose of 0.4 mg/kg b.w. Group II was treated with an oral paste formulation of ivermectin at the recommended dose of 0.2 mg/kg b.w. Faecal samples were collected at different times between 1 and 75 days ...
Levine DG, Epstein KL, Ahern BJ, Richardson DW.To determine (1) if clinically useful concentrations of amikacin sulfate can be obtained in synovial fluid during regional limb perfusion (RLP) performed above the carpus in standing sedated horses and (2) to determine the efficacy of 3 tourniquet types (narrow rubber [NR], wide rubber [WR], pneumatic [PN]). Methods: Horses (n=9). Methods: Bilateral forelimb RLP with amikacin sulfate (2.5 g) were administered through the cephalic vein in standing sedated horses. Limbs were randomly assigned to the 3 tourniquet types (NR, WR, PN) applied above the carpus. Metacarpophalangeal synovial fluid was ...
Lavoie JP, Leclere M, Rodrigues N, Lemos KR, Bourzac C, Lefebvre-Lavoie J, Beauchamp G, Albrecht B.Corticosteroids are the most potent drugs for the control of severe equine asthma, but adverse effects limit their chronic systemic administration. Inhaled medications allow for drug delivery directly into the airways, reducing the harmful effects of these drugs. Objective: To evaluate the efficacy of inhaled budesonide specifically formulated for the equine use and administered by a novel inhalation device in horses with severe asthma. Methods: Experimental studies in horses with naturally occurring asthma with cross-over, randomised, blinded experimental designs. Methods: In Study 1, budeson...
Lavoie JP, Pasloske K, Joubert P, Cordeau ME, Mancini J, Girard Y, Friesen RW, Frenette R, Blouin M, Young RN, Hickey G.Phosphodiesterase-4 (PDE 4) enzyme inhibitors have been shown to have anti-inflammatory properties in various animal disease processes and therefore could be effective drugs for the treatment of equine airway diseases. The purpose of this study was to evaluate the efficacy and adverse effects of the PDE 4 inhibitor L-826,141 in horses with heaves. In a blinded parallel design, horses with heaves exposed daily to moldy hay were given a placebo for 14 days and then administered either L-826,141 (n = 6; loading dose of 1 mg/kg IV followed by 0.5 mg/kg IV q48h) or dexamethasone (n = 6; 0.04 mg/kg ...
Tomlinson JE, Blikslager AT.Recent studies have shown that flunixin prevented recovery of equine jejunum post ischaemia. However, the use of a purported cyclooxygenase (COX)-2 preferential inhibitor, etodolac, also prevented recovery. These findings may have implications for the use of nonsteroidal anti-inflammatory drugs in colic patients. Objective: To compare the effects of deracoxib, a highly selective canine COX-2 inhibitor, with flunixin on in vitro recovery of ischaemic-injured equine jejunum. Methods: Six horses underwent 2 h jejunal ischaemia, after which mucosa was mounted in Ussing chambers and recovered for 2...
Gokbulut C, Nolan AM, McKellar QA.The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) w...
Vandeweerd JM, Zhao Y, Nisolle JF, Zhang W, Zhihong L, Clegg P, Gustin P.Intra-articular (IA) corticosteroids (CS) have been used in the treatment of osteoarthritis for many years, although their effects on articular cartilage are not fully understood. To identify whether previous animal studies have provided enough evidence about the effects of CS, we undertook a systematic review that identified 35 relevant in vivo animal experimental studies between 1965 and 2014 assessing the effects of CS on either normal cartilage, or in either induced osteoarthritis (OA) or synovitis. The quality of the methodology was assessed. Deleterious effects, both structural and bioc...
Knych HK, Baden RW, Gretler SR, McKemie DS.Despite their widespread popularity as sport and companion animals and published and anecdotal reports of vast difference in drug disposition and pharmacokinetics between individuals, studies describing equine drug metabolism are limited. It has been theorized that similar to humans, members of the CYP2D family in horses may be polymorphic in nature leading to differences in metabolism of substrates. This study aims to build on the limited current knowledge regarding P450 mediated metabolism in horses by describing the metabolism of the polymorphic CYP2D6 probe drug codeine in vitro. Codeine, ...
Bettschart-Wolfensberger R, Freeman SL, Bowen IM, Aliabadi FS, Weller R, Huhtinen M, Clarke KW.Currently available sedatives depress cardiopulmonary function considerably; therefore, it is important to search for new, less depressive sedatives. The study was performed to assess duration and intensity of cardiopulmonary side effects of a new sedative, dexmedetomidine (DEX), in horses. Objective: To study pharmacokinetics and cardiopulmonary effects of i.v. DEX. Methods: Pharmacokinetics of 3.5 microg/kg bwt i.v. DEX were studied in a group of 8 mature (mean age 4.4 years) and 6 old ponies (mean age 20 years). Cardiopulmonary data were recorded in mature ponies before and 5, 10, 20, 30, 4...
Sinclair MD, Mealey KL, Matthews NS, Peck KE, Taylor TS, Bennett BS.To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species. Methods: 5 clinically normal horses and 5 clinically normal donkeys. Methods: Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinet...
Tobin T, Chay S, Kamerling S, Woods WE, Weckman TJ, Blake JW, Lees P.Phenylbutazone is an acidic, lipophilic, non-steroidal anti-inflammatory drug (NSAID). It is extensively metabolized in the horse. The metabolites so far identified, oxyphenbutazone, gamma-hydroxyoxyphenbutazone, account for some 25-30% of administered dose over 24 h. The plasma half-life of phenylbutazone and termination of its pharmacological action are determined primarily by its rate of hepatic metabolism. Phenylbutazone acts by inhibiting the cyclooxygenase enzyme system, which is responsible for synthesis of prostanoids such as PGE2. It appears to act on prostaglandin-H synthase and pros...
Valverde A.Balanced anesthetic techniques are commonly used in equine patients, and include the combination of a volatile anesthetic with at least one injectable anesthetic throughout the maintenance period. Injectable anesthetics used in balanced anesthesia include the α2-agonists, lidocaine, ketamine, and opioids, and those with muscle-relaxant properties such as benzodiazepines and guaifenesin. Administration of these injectable anesthetics is best using constant-rate infusions based on the pharmacokinetics of the drug, which allows steady-state concentrations and predictable pharmacodynamic actions....
Gustafsson A, Båverud V, Franklin A, Gunnarsson A, Ogren G, Ingvast-Larsson C.Six healthy adult horses were given repeated administrations of trimethoprim/ sulfadiazine (TMP/SDZ) intravenously (i.v.) (2.5 mg/kg TMP and 12.5 mg/kg SDZ) and orally (p.o.) as a paste (5 mg/kg TMP and 25 mg/kg SDZ). Both formulations were given twice daily for 5 days, with a 3-week interval between i.v. and oral administration. The influence of the drug combination on the intestinal microflora was examined and the plasma concentrations, pharmacokinetic parameters and plasma protein binding were determined. There were no major changes in the bacterial intestinal flora and no clinical evidence...
Saps M, Miranda A.There is little evidence for most of the medications currently used to treat functional abdominal pain disorders (FAPDs) in children. Not only are there very few clinical trials, but also most have significant variability in the methods used and outcomes measured. Thus, the decision on the most appropriate pharmacological treatment is frequently based on adult studies or empirical data. In children, peppermint oil, trimebutine, and drotaverine have shown significant benefit compared with placebo, each of them in a single randomized clinical trial. A small study found that cyproheptadine was be...
Lees P, Landoni MF.Carprofen is a nonsteroidal anti-inflammatory drug of the 2-arylpropionate subclass. It contains a single chiral centre and exists in two enantiomeric forms. In this study rac-carprofen, at two dosages, 0.7 and 4.0 mg/kg, and placebo were administered i.v. to six New Forest horses in a three period cross-over study. The concentration-time profiles were established for R(-) and S(+)-carprofen for plasma and both inflamed (exudate) and noninflamed (transudate) tissue cage fluids. R(-)-carprofen was the predominant enantiomer in all three fluids, as indicated by plasma area under the curve (AUC) ...
Firth EC, Nouws JF, Driessens F, Schmaetz P, Peperkamp K, Klein WR.The plasma penicillin concentrations were determined in 5 horses given an IV injection of sodium penicillin G; plasma penicillin concentrations were also determined in a crossover experiment, where animals were given procaine penicillin G subcutaneously at 1 site and IM at 4 sites. The mean penicillin plasma peak concentration and bioavailability were highest after the drug was injected in the neck and biceps musculature. Injections in the gluteal muscle and in the subcutaneous sites resulted in similar, but lower, more persistent penicillin plasma concentrations and a lower bioavailability th...
Kelmer G, Bell GC, Martin-Jimenez T, Saxton AM, Catasus C, Elliot SB, Meibohm B.Previous studies have shown that regional limb perfusion (RLP) using the palmar digital (PD) vein delivers therapeutic concentration of amikacin to the distal limb. Our hypothesis was that using the cephalic and saphenous veins for RLP will enable delivery of therapeutic concentrations of amikacin to the distal limb. Nineteen healthy horses participated in the study. The cephalic, saphenous, or PD vein was used to perfuse the limb with amikacin. Two grams of amikacin was used for RLP using the saphenous and the cephalic veins, and one gram was used in the PD vein. Synovial samples were collect...
Meyer S, Giguère S, Rodriguez R, Zielinski RJ, Grover GS, Brown SA.The objectives of this study were to determine pharmacokinetics of intravenous (i.v.) ceftiofur in foals, to compare ultra-high performance liquid chromatography tandem mass spectometry (UPLC-MS/MS) and microbiologic assay for the measurement of ceftiofur concentrations, and to determine the minimum inhibitory concentration (MIC) of ceftiofur against common equine bacterial pathogens. In a cross-over design, ceftiofur sodium was administered i.v. to six foals (1-2 days-of-age and 4-5 weeks-of-age) at dosages of 5 and 10 mg/kg. Subsequently, five doses of ceftiofur were administered i.v. to six...
Steffey EP, Eisele JH, Baggot JD.To quantitate dose- and time-related magnitudes of interactive effects of morphine (MOR) and isoflurane (ISO) in horses and to characterize pharmacokinetics of MOR in plasma and the ventilatory response to MOR during administration of ISO. Methods: 6 adult horses. Methods: Horses were anesthetized 3 times to determine the minimum alveolar concentration (MAC) of ISO in O2 and then to characterize the change in anesthetic requirement as defined by the alteration in ISO MAC following IV administration of saline (0.9% NaCl) solution and 2 doses of MOR (low dose, 0.25 mg/kg; high dose, 2.0 mg/kg). ...
Muir WW, Sams RA, Huffman RH, Noonan JS.The cardiopulmonary, behavioral, and pharmacokinetic properties of diazepam were determined in horses. Heart rate, cardiac output, mean pulmonary artery, aortic and right atrial blood pressures, respiratory rate, and arterial pH and blood gas values did not change after IV diazepam (0.05, 0.1, 0.2, 0.4 mg/kg) administration. Increasing doses of diazepam resulted in signs of muscle weakness including fixed stance, muscle fasciculations of the head, neck, and thorax muscles, ataxia, and then recumbency. Dosages of diazepam exceeding 0.2 mg/kg produced mild sedation. Behavioral changes persisted ...
Kaka JS, Klavano PA, Hayton WL.Ketamine HCl was administered IV to xylazine HCl-treated horses. The plasma concentration of ketamine was measured several times after administration of the drug and these data were used to develop a two-compartment pharmacokinetic model. The distribution and the elimination phase half-lives averaged 2.9 and 42 minutes. The volume of the central compartment averaged 212 ml/kg of body weight and the volume of the peripheral compartment was approximately threefold larger. The total body clearance of ketamine averaged 26.6 ml/minute/kg. Plasma protein binding of ketamine averaged 50% over the con...
Toutain PL, Brandon RA, de Pomyers H, Alvinerie M, Baggot JD.Pharmacokinetics of dexamethasone and prednisolone were studied in 6 horses given dexamethasone alcohol (IV or IM) or dexamethasone 21-isonicotinate as a solution IV or IM (50 micrograms/kg of body weight), prednisolone 21-sodium succinate IV or IM (0.6 mg/kg of body weight), or prednisolone acetate IM (0.6 mg/kg of body weight). Plasma concentrations were determined using a high-performance liquid chromatographic method. After dexamethasone alcohol (IV) or dexamethasone 21-isonicotinate (IV), the half-life of elimination was similar (53 minutes) for both formulations. After dexamethasone (alc...
Hart KA, Dirikolu L, Ferguson DC, Norton NA, Barton MH.To compare daily endogenous cortisol production rate and the pharmacokinetics of an i.v. bolus of hydrocortisone between neonatal foals and adult horses. Methods: 10 healthy full-term 2- to 4-day-old foals and 7 healthy adult horses. Methods: Blood samples were collected from each horse every 15 to 20 minutes for 24 hours for determination of 24-hour mean cortisol concentration. Afterward, dexamethasone (0.08 mg/kg) was administered i.v. to suppress endogenous cortisol production. Twelve hours afterward, hydrocortisone sodium succinate (1.0 mg/kg) was administered as a rapid i.v. bolus and ser...
Natalini CC.In the past 10 years, there have been many recent advances in spinal techniques in horses, both epidural and subarachnoid, to identify drugs or drug combinations that have sensory effects without motor nerve paralysis, thus providing pain control without these horses becoming recumbent. Opioids, alpha-2 agonists, dissociative drugs, and others have been investigated. Many of these drugs, which have serious side effects when injected systemically in horses, have been shown to have useful analgesic effects when injected spinally. Morphine-like opioids have the greatest potential for spinal use a...
Mendoza FJ, Perez-Ecija A, Toribio RE.Donkeys and mules show several pharmacodynamic and pharmacokinetic idiosyncrasies that have to be fully considered by any clinician dealing with these species. Because they possess an increased metabolic rate and cellular water content compared with horses, higher doses (or shorter dosing intervals) are usually recommended for those drugs where pharmacologic studies have been performed. Nonetheless, owing to the lack of species-specific information, this assumption cannot be arbitrarily applied. Thus, when a drug protocol published for horses is extrapolated to a donkey or a mule, a close moni...
Ensink JM, Klein WR, Mevius DJ, Klarenbeek A, Vulto AG.The pharmacokinetics of ampicillin and amoxicillin following intravenous administration at a dose rate of 15 and 10 mg/kg respectively were studied in four healthy adult horses. Pharmacokinetics of pivampicillin and amoxicillin were studied after oral administration to four healthy adult horses. Pivampicillin, a prodrug of ampicillin, was administered orally to starved and fed horses at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Amoxicillin was administered orally to starved horses only, at a dose rate of 20 mg/kg. Ampicillin and amoxicillin con...
Brown RF, Houpt KA, Schryver HF.In two adult horses doses of 0.02-0.03 mg/kg diazepam, intravenously, increased 1 hr intake 54-75% above control levels. Intake was stimulated when the diet was a high grain, calorically dense one and also when the diet was a high fiber, calorically dilute one. Two young rapidly growing weanling horses showed an even more pronounced stimulation of intake. Following diazepam 1 hr intake was increased 105-240% above control lelvels. Promazine at a dose of 0.5 mg/kg also stimulated intake in adult horses, but not as markedly as did diazepam. A transquilizer and a neuroleptic appear to have a stim...
Fuchs S, Klier J, May A, Winter G, Coester C, Gehlen H.Delivering active ingredients using biocompatible and biodegradable carriers such as gelatin nanoparticles (GNPs) to the lung constitutes a promising non-invasive route of administration. However, the pulmonary delivery of nanoparticle-based immunotherapy is still a field that requires more clarification. In this study, GNPs loaded with cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN)-loaded and plain GNPs were aerosolised either by a conventional pressured metered dose inhaler (pMDI) or by active or passive vibrating-mesh (VM) nebulisers. GNP sizes after nebulisation by active and p...
