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.
Hagedorn HW, Zuck S, Schulz R.The azaphenothiazine neuroleptic prothipendyl (Dominal) is suspected to be administered illegally at low doses to race-horses to improve their performance. Since for this species pharmacokinetic data of the drug are missing we studied its elimination from blood and urine in a standard-bred mare. At a low (subtherapeutic) dose (i.v., 0.24 mg/kg) the horse is described to be less excited while locomotor activity and attention remain unaffected. In contrast, sedation and ataxia are brought about at 1 mg/kg (therapeutic dose). Identification of prothipendyl given i.v. at subtherapeutic doses was a...
Mama KR, Steffey EP, Pascoe PJ.To evaluate selected hemodynamic, respiratory, and behavioral responses to propofol in horses premedicated with xylazine or detomidine. Methods: Xylazine (0.5 and 1.0 mg/kg of body weight) was administered IV on different days to each of 6 horses prior to IV administration of propofol (2 mg/kg). In a second group of 6 horses, detomidine (15 and 30 micrograms/kg) was similarly studied. Methods: 2 groups of 6 mature healthy horses. Methods: Rectal temperature, heart and respiratory rates, arterial blood gas tensions, and direct arterial blood pressures were recorded before and at fixed intervals...
Riddolls LJ, Byford GG, McKee SL.The biological and imaging characteristics of technetium-99m imidodiphosphate (Tc99m-IDP) were measured in 4 horses once and in 1 horse twice. All computational results are expressed with 95.5% (mean +/- 2 SD) confidence limits. The clearance half-time of the radiopharmaceutical from the blood was 29.6 +/- 2.3 min. The percentage of the administered dose circulating in the whole-blood volume at 4 h was 3.9 +/- 0.8%. The Tc99m-IDP radioactivity confined at the plasma fraction of the whole blood at 4 h was 85.3 +/- 1.6%. At 8 h, approximately 45 +/- 16% of the dose administered had been excreted...
Harkins JD, Mundy GD, Stanley S, Woods WE, Boyles J, Arthur RA, Sams RA, Tobin T.Plasma and urinary concentrations of procaine and the duration of response to procaine after its administration as a local anaesthetic to horses were studied. Following injection of a clinical dose of procaine HCl (80 mg), the concentration of procaine in plasma was less than the lower limit of quantitation and unsuitable for threshold determination. Therefore, the urinary concentration of procaine was determined after injection of a dose of 5 mg procaine HCl, the highest no-effect dose (HNED) of this agent. Free unconjugated procaine in equine urine reached a peak concentration of 23.7 ng/mL,...
Jarvis GE, Evans RJ.Endotoxin has previously been shown to induce platelet aggregation in equine heparinised whole blood. This study aimed to determine whether platelet-activating factor or products of cyclo-oxygenase metabolism (thromboxane A2 or prostaglandins) were important in mediating the response of platelets to endotoxin. The effects of the following drugs on endotoxin-induced aggregation were investigated: aspirin, flunixin meglumine and carprofen (non-steroidal anti-inflammatory drugs); CV-3988 and WEB2086 (platelet-activating factor receptor antagonists); quinacrine (phospholipase A2 inhibitor). The ef...
Lloyd DR, Rose RJ, Duffield AM, Suann CJ.The combination of large doses of sodium bicarbonate and the potent narcotic, etorphine, has reportedly been given to racehorses in attempts to improve their performance and also to "mask" the presence of etorphine in urine samples. The increased urinary output and pH associated with sodium bicarbonate (approximately 500 g) administration may reduce the urinary concentration of etorphine, making it more difficult to detect. Our experiment was designed to examine the effects of this combination. Six Thoroughbred horses were used in a latin-square design with three horse pairs and three treatmen...
Aida H, Mizuno Y, Hobo S, Yoshida K, Fujinaga T.The effects of 1.0, 1.5, and 2.0 minimum alveolar concentration (MAC) of sevoflurane on hemodynamic, pulmonary and blood chemistry variables were measured during spontaneous and controlled ventilation in healthy horses. Sevoflurane was the only anesthetic drug administered to the horses. In a dose-dependent manner, sevoflurane significantly decreased (P < .05) mean arterial blood pressure, cardiac output, and stroke volume. There was a progressive decrease in peripheral vascular resistance and an increase in heart rate as the concentration of sevoflurane was increased, but the differences w...
Orsini JA, Park MI, Spencer PA.Concentrations of amikacin in endometrial tissue and plasma were studied in mares in estrus after intrauterine infusion of 1.0 or 2.0 g once a day for 3 consecutive d, and after 9.7 or 14.5 mg/kg body weight (BW) had been injected intramuscularly once a day for 3 consecutive d to determine concentrations of amikacin sulfate in plasma and endometrial tissues, and whether parenteral administration provides any advantages over intramuscular infusion. No amikacin was detected in serum at the 1.0 g dose. At the infusion dose of 2.0 g once a day, very low levels of serum amikacin were detected at 1 ...
Kristinsson J, Thordarson TH, Johannesson T.The pharmacokinetics of lignocaine was studied in four Icelandic horses after infiltration anaesthesia. A total of 240 mg of the drug was injected on either side of the left foreleg, over the medial and lateral branches of the palmar nerve. Blood samples were collected up to seven hours after injection and the concentrations of the drug in plasma were determined by gas chromatography/mass spectrometry. The results showed that lignocaine was rapidly absorbed. A mean maximum concentration of 232 ng/ml was observed after 20 minutes. In three of the horses the decline in the plasma concentration o...
Lillich JD, Bertone AL, Schmall LM, Ruggles AJ, Sams RA.OBJECTIVE--To document plasma, urine, and synovial fluid disposition of 2 common intra-articularly administered steroid preparations, methylprednisolone acetate (MPA) and isoflupredone acetate (IPA). DESIGN--Descriptive investigation. SAMPLE POPULATION--100 mg of MPA or 4 mg of IPA was administered to 2 groups of 4 healthy sound radiographically normal female horses. PROCEDURE--Blood samples were collected at time 0 (before) and 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after administration of the designated steroid. Complete urine collection for measurement of designated steroid was ac...
Soraci AL, Mestorino ON, Errecalde JO.The pharmacokinetics and bioavailability of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase (t1/2 (alpha): 4.22 +/- 2.73 min) was followed by a slower elimination phase (t1/2(beta) 0.77 +/- 0.19 h). The apparent volume of distribution was 0.68 +/- 0....
Chen CL, Zhu D, Gillis KD, Meleka-Boules M.To develop a simple and sensitive ELISA for detection of dexamethasone in horse serum and urine. Methods: Blood and urine samples from 3 thoroughbred mares. Methods: A dexamethasone oxime was prepared and conjugated to hemocyanin, bovine serum albumin and to horseradish peroxidase. One- and two-step double-antibody ELISA methods, as well as a radioimmunoassay method, were performed. The one-step ELISA was used to test urine from 3 Thoroughbred mares injected with 5 mg of dexamethasone, IV. Results: The ELISA could detect dexamethasone in the range of 0.01 to 50 ng/ml, with intra- and interassa...
Soraci A, Jaussaud P, Benoit E, Delatour P.Fenoprofen (FPF) is a chiral non-steroid antiinflammatory drug, marketed as a racemic mixture of its R(-) and S(+) enantiomers. Its stereoselective disposition in humans and animals is due to a chiral inversion converting R(-)FPF into S(+)FPF. The first step of this reaction, which produces an acyl-CoA thioester, is catalysed by an acyl-CoA ligase. A stereospecific high performance liquid chromatography assay was used to study the disposition of FPF enantiomers in four geldings and three male beagle dogs, following intravenous doses of racemic FPF (1 mg/kg in horses), R(-)FPF (0.5 mg/kg in hor...
Lindholm A, Ronéus B, Lindblad G, Jones B.The biological turnover of hyaluronan (sodium hyaluronate) of different molecular weights (0.6 x 10(6) and 2.5 x 10(6) Daltons) was studied in the synovial fluid of the middle carpal and metacarpophalangeal joints of 6 clinically healthy Standardbred horses. The hyaluronan was radioactively labelled with 14C. The biological half-life (t1/2) was calculated from repeated synovial samples after injection of the labelled hyaluronan. The mean t1/2 in the metacarpophalangeal joints was 9.7 h for low molecular weight hyaluronan and 8.9 h for high molecular weight hyaluronan and in the middle carpal j...
Sams RA, Gerken DF, Detra RL, Stanley SD, Wood WE, Tobin T, Yang JM, Tai HH, Jegananthan A, Watt DS.Two metabolites of the tranquilizer azaperone were extracted from alkalinized horse urine after treatment with beta-glucuronidase/sulfatase from limpets (Patella vulgata). The metabolites were identified by a combination of independent chemical synthesis and GC/MS and 1H NMR analysis. The metabolites were identified as 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1-piperazinyl]-1-butanol, designated as 5'-hydroxy-azaperol, and 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1-piperazinyl]-1-butanone, designated as 5'-hydroxyazaperone. A TLC screening test was developed for detecting both metabo...
Ensink JM, Moi A, Vulto AG, Tukker JJ.Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses. Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only. The dose of pivampicillin was 19.9 mg/kg, and the dose of ampicillin trihydrate was 17 mg/kg. Both doses are equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 24 hours after administration. After administration of pivampicillin to starved and fed horses the...
Miller MA, Honstead JP, Lovell RA.The fumonisins are a recently discovered class of mycotoxins produced primarily by Fusarium (F.) moniliforme and F. proliferatum. Fumonisins present in mycotoxin-contaminated feed have been identified as the causative agent of equine leukoencephalomalacia and porcine pulmonary edema. To prevent these diseases, FDA has utilized informal guidance levels for fumonisins in feed and initiated a surveillance program for fumonisins in feed corn and corn by-products during FY 93 and 94. Natural contaminants present in animal feed can enter the human food supply as residues present in animal tissues an...
Smith RF, Jackson LS, Moore A.An 125I radioimmunoassay to determine the pattern of urinary excretion of etorphine (a semisynthetic opiate agonist) after its administration to horses is described. Three thoroughbred horses were each given 5, 15, 30 and 100 micrograms of etorphine intramuscularly. Urine was collected for up to 72 after administration. The maximum etorphine concentration after administration of a dose of 5 micrograms was 711 pg ml-1 (concentrations were greater than 100 pg ml-1 after 23 h in all three horses); a 15 micrograms gave 2661 pg ml-1 (levels remained above 100 pg ml-1 for more than 44 h in each hors...
Littlewood JD, Rose JF, Paterson S.A single blind controlled clinical trial of oral ivermectin paste at a dose rate of 0.1 mg/kg daily for seven days for the treatment of chorioptic mange in horses was carried out. There was a statistically significant reduction in the numbers of mites in the samples taken from the treated horses compared with the untreated horses, but the mites were not eliminated from all the treated animals. Two further groups of horses were treated, one at a dose rate of 0.1 mg/kg daily for 10 days and the other with two doses of 0.2 mg/kg given two weeks apart. There were no statistically significant diffe...
Steiner A, Roussel AJ.Hypodynamic gastrointestinal disorders in horses and cattle that are thought to benefit from treatment with drugs restoring and coordinating gastrointestinal motility include postoperative ileus and large colon impaction in the horse and displacement of the abomasum and dilatation of the cecum in cattle. Important physiologic, pathophysiologic and pharmacologic mechanisms involved in the intrinsic control of gastrointestinal motility include cholinergic, adrenergic, dopaminergic, serotoninergic, and opioid-mediated pathways. Preliminary results suggest that cisapride, acting on 5-Hydroxytrypta...
Mills PC, Dunnett M, Smith NC.The pharmacokinetics of oral and intravenous allopurinol was studied in five horses and compared with intravenous oxypurinol. The plasma concentration vs. time curves, following intravenous administration of 5 mg/kg, were best described by the biexponential equations Cp = 106.58e(-25.14t) + 159.93e(-10.96t) for allopurinol and Cp = 321.09e(-9.72t) + 82.39e(-0.44t) for oxypurinol, with an elimination half-life (t1/2 beta) of 0.09 h and an area under the curve (AUC) of 19.8 mumol.h/L after intravenous administration, while the t1/2 beta and AUC of oxypurinol were 1.09 h and 231 mumol.h/L, respec...
Landoni MF, Lees P.The bioavailability of S(+) and R(-) ketoprofen (KTP) in six horses was investigated after oral administration of the racemic (rac) mixture. Two oral formulations were studied, an oil-based paste containing micronised rac-KTP and powder from the same source in hard gelatin capsules, each at a dose rate of 2.2 mg/kg. For the oil-based paste two feeding schedules were used; horses were either allowed free access to food or access to food was restricted for 4 h before and 5 h after dosing. The drug in hard gelatin capsules was administered to horses with restricted access to food. After intraveno...
van der Kolk JH, Wisse H, van Dijk S.A 20-year-old Arab crossbred gelding was examined because it had apparently suffered an overstimulation of the parasympathetic nervous system for three hours. The clinical signs consisted of hypersalivation, profuse sweating, maximal miosis, fasciculation of the muscles and lateral recumbency in combination with continuous convulsions without diarrhoea. The horse's plasma pseudocholinesterase activity was approximately 10 per cent of normal. It responded well to 10 mg atropine and 50 mg diazepam administered intravenously.
van Duijkeren E, Sloet van Oldruitenborgh-Oosterbaan MM, Vulto AG, Kessels BG, van Miert AS, Breukink HJ.The pharmacokinetic parameters of a powder formulation of trimethoprim/sulphachlorpyridazine were studied in eight healthy horses which received 5 mg/kg trimethoprim and 25 mg/kg sulphachlorpyridazine 12-hourly with concentrate for five days. The intake of the medicated concentrate by the horses was variable during the first two days, but after they became accustomed to the taste the intake by all the horses during the last three days was good. Faecal samples taken before and on the last day of the drug administrations were negative when cultured for salmonella. Compared with the results of a ...
Sarasola P, McKellar QA.Bacampicillin hydrochloride is an ester prodrug that is hydrolyzed to ampicillin after its absorption from the gastrointestinal tract. It was administered intragastrically at a dose rate of 13.5 mg/kg of body weight to ponies and horses, and was highly bioavailable (F = 41.0%), compared with other penicillins in adult horses. The high peak ampicillin plasma concentration of 6.1 +/- 0.5 micrograms/ml achieved and persistence of the antibiotic at concentration of 0.3 +/- 0.1 microgram/ml 6 hours after its intragastric administration, suggest that bacampicillin hydrochloride may reach suitable ba...
Valdez RA, DiPietro JA, Paul AJ, Lock TF, Hungerford LL, Todd KS.The bioequivalence of Strongid C and generic pyrantel tartrate was determined in a controlled study using 30 horses with naturally acquired endoparasitic infections. Three horses were randomly allocated to each of ten replicates based on quantitative nematode and ascarid egg counts and fecal larvae culture results. Horses within each replicate were randomly assigned to one of three treatment groups. Horses in Treatment Group 1 received only oats; horses in Treatment Group 2 received generic pyrantel tartrate pellets (2.65 mg pyrantel tartrate kg-1) mixed with oats; horses in Treatment Group 3 ...
Credille BC, Giguère S, Berghaus LJ, Burton AJ, Sturgill TL, Grover GS, Donecker JM, Brown SA.The objectives of this study were to determine the plasma and pulmonary disposition of ceftiofur crystalline free acid (CCFA) in weanling foals and to compare the plasma pharmacokinetic profile of weanling foals to that of adult horses. A single dose of CCFA was administered intramuscularly to six weanling foals and six adult horses at a dose of 6.6 mg/kg of body weight. Concentrations of desfuroylceftiofur acetamide (DCA) were determined in the plasma of all animals, and in pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells of foals. After intramuscular (IM) admin...
Ishii H, Shibuya M, Leung GN, Yamashita S, Nagata SI, Kushiro A, Sakai S, Toju K, Okada J, Kawasaki K, Kusano K, Kijima-Suda I.For the purpose of doping control, this is the first report of accurate quantification of four critical structural isomers of nicotine metabolites (trans-3'-hydroxycotinine, cis-3'-hydroxycotinine, 5'-hydroxycotinine, and N'-hydroxymethylnorcotinine) in equine plasma and urine for the establishment of their elimination profiles. Besides, the pharmacokinetic studies of trans-3'-hydroxycotinine and N'-hydroxymethylnorcotinine in equine plasma and urine are also presented for the first time. Methods: The accurate quantification methods of the aforementioned four structural isomers in horse plasma...
de Haas GH, Dijkman R, Lugtigheid RB, Dekker N, Van den Berg L, Egmond MR, Verheij HM.The inhibitory power (Z) of a number of (R)-1-alkyl-2-acylamino phospholipid analogues was determined for three mammalian phospholipases A2 from pig, ox and horse pancreas. All three enzymes display a clear preference for anionic (phosphoglycol) inhibitors over the zwitterionic (phosphocholine) derivatives; this effect is most pronounced for the bovine enzyme. Upon variation of the 1-alkyl chain length, the bovine and equine phospholipases, like the porcine enzyme in previous studies, show an optimum in Z for a six-carbon alkyl group. The introduction of a double bond in the 2-acylamino group ...
Bidwell LA, Wilson DV, Caron JP.To measure concentrations of lidocaine serum after application of two 5% patches on horses. Methods: Prospective experimental trial Methods: Six client-owned, systemically healthy horses. Methods: The hair was clipped on the medial aspect above the carpus of both fore limbs and 2 patches of 5% lidocaine were applied within 30 minutes of jugular catheter placement and the area was then bandaged. Venous blood was drawn from a jugular vein catheter that was inserted using lidocaine as a local block. Samples were drawn immediately before and at 2, 4, 6, 8, and 12 hours after patch application. The...
Beech J, Lindborg S.Horses with hyperkalaemic periodic paralysis were challenged with an oral dose of potassium chloride, and the prophylactic efficacy of phenytoin, acetazolamide and hydrochlorothiazide was evaluated, with at least three weeks separating the trials of each drug. After the administration of potassium chloride without prophylactic medication the horses' clinical signs ranged from generalised fine muscle fasciculations to gross tremors, and weakness with occassional prolapse of the nictitating membrane; plasma potassium concentration increased significantly (P < 0.01) from 4.0 +/- 0.2 to 6.0 +/-...
Gonzalez GA, Betbeze C, Wills R, Eddy A, Mochal-King C, Fontenot RL.To evaluate corneal sensitivity and adverse events following subconjunctival administration of three local anesthetics in horses. Methods: Randomized, masked, crossover study. Methods: Twelve healthy adult mares. Methods: The subconjunctival space of the treated eye was injected with 0.2 mL of liposomal bupivacaine (1.3%), ropivacaine (0.5%), or mepivacaine (2%). All horses received each medication once and the contralateral eye received saline (control). Corneal touch threshold (CTT) was measured using a Cochet-Bonnet esthesiometer before sedation, after sedation, and at specified intervals...
van der Woerdt A, Gilger BC, Wilkie DA, Strauch SM, Orczeck SM.To determine normal variation in, and effect of 2% pilocarpine hydrochloride on, intraocular pressure (IOP) and pupil size in female horses during a specified period. Methods: 10 female horses with normotensive eyes. Methods: IOP and horizontal and vertical pupil size were measured on a single day between 8 AM and 8 PM at hours 0, 0.5, 1, 2, 4, 6, 8, 10, and 12. Measurements were repeated after single- dose application of 2% pilocarpine to both eyes. IOP and pupil size were measured at 8 AM and noon in a 5-day experiment of twice-daily application of 2% pilocarpine. Results: Variation in IOP a...
Hunyadi L, Datta P, Rewers-Felkins K, Sundman E, Hale T, Fajt V, Wagner S.The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528 kg were administered a single dose of 0.5 mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15 min, 30 min, 45 min, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one-compartment model. Mean C was 486 ng/ml (range 423-549...
Edwards SH, Khalfan SA, Jacobson GA, Pirie AD, Raidal SL.OBJECTIVE To determine plasma drug concentrations after IV administration of a bolus followed by continuous rate infusion (CRI) of sodium benzylpenicillin and ceftiofur sodium to healthy adult horses. ANIMALS 6 Thoroughbred mares (3 to 9 years old; mean ± SD body weight, 544 ± 55 kg) with no history of recent antimicrobial treatment. PROCEDURES Horses were used in 2 experiments conducted 14 days apart. For each experiment, horses were housed individually in stables, and catheters were placed bilaterally in both jugular veins for drug administration by CRI (left catheter) and for intermittent...
Engelking LR, Dodman NH, Hartman G, Valdez H.The acute 2-hour effects of isoflurane anesthesia on liver function and biliary excretion were examined in 2 ponies prepared surgically with chronic external biliary fistulas (T-tubes). Studies were conducted 2 to 8 months postoperatively with the enterohepatic circulation held intact between studies. Bile acid infusion IV (8.1 to 8.8 mumol/min) helped maintain bile flow and bile acid and bilirubin excretion during complete biliary diversion throughout each study. Following 3-hour control periods, anesthesia was induced and maintained at 1.3 to 1.5 minimal alveolar concentration plus O2 (spont...
Gokbulut C, Ozuicli M, Aksit D, Aksoz E, Korkut O, Yalcinkaya M, Cirak VY.The horse milk gains increasing interest as a food product for sensitive consumers, such as children with food allergies or elderly people. We investigated the plasma and milk disposition, faecal excretion and efficacy of per os ivermectin (IVM) and pour-on eprinomectin (EPM) in horses. Ten mares were divided into two groups. The equine paste formulation of IVM and bovine pour-on formulation of EPM were administered orally and topically at dosage of 0.2 and 0.5 mg/kg bodyweight. Blood, milk and faecal samples were analysed using high-performance liquid chromatography. The plasma concentration...
Dunnett M, Richardson DW, Lees P.Hair analysis to detect drug administration has not been studied extensively in horses. This study aimed to (a) develop an analytical method for enrofloxacin and its metabolite ciprofloxacin in mane and tail hair, (b) relate measured values to doses, routes of administration, hair colour, and (c) demonstrate long-term detectability. Samples were extracted in trifluoroacetic acid at 70 degrees C. Extracts were cleaned-up by solid-phase extraction and analysed by high-performance liquid chromatography with UV-diode array detection. Analyte recoveries were > 87%. Horses were sampled after therape...
Ewing PJ, Burrows G, MacAllister C, Clarke C.The pharmacokinetic properties of four erythromycin formulations were compared in six adult horses after administration of single and multiple oral doses. Formulations of erythromycin administered were estolate and phosphate given 37.5 mg/kg every 12 h and 25 mg/kg every 8 h, and stearate and ethylsuccinate given 25 mg/kg every 8 h. Areas under the curve (AUC) and maximum plasma erythromycin concentrations (Cmax) were equal or greater (P > or = 0.05) following administration of erythromycin phosphate and stearate compared with those values following administration of erythromycin estolate or e...
Bailly-Chouriberry L, Garcia P, Cormant F, Loup B, Popot MA, Bonnaire Y.Cobra (Naja naja kaouthia) venom contains a toxin called α-cobratoxin (α-Cbtx) containing 71 amino acids (MW 7821 Da) with a reported analgesic power greater than morphine. In 2013, the first analytical method for the detection of α-Cbtx in equine plasma was developed by Bailly-Chouriberry et al, allowing the confirmation of the presence of α-Cbtx at low concentrations (1-5 ng/mL or 130-640 fmol/mL) in plasma samples. To increase the method sensitivity and therefore to improve the detection of α-Cbtx in post-administration plasma samples, a nano-liquid chromatography-mass spectrometry/hi...
Sandbaumhüter FA, Theurillat R, Bettschart-Wolfensberger R, Thormann W.The combination of ketamine and an α -receptor agonist is often used in veterinary medicine. Four different α -receptor agonists, medetomidine, detomidine, xylazine, and romifidine, which differ in their chemical structure and thus in selectivity for the α -receptor and in the sedative and analgesic potency, are typically employed during surgery of equines. Recovery following anesthesia with ketamine and an α -receptor agonist is dependent on the α -receptor agonist. This prompted us to investigate (i) the inhibition characteristics for the N-demethylation of ketamine to norketamine and (...
Colahan PT, Bailey JE, Chou CC, Johnson M, Rice BL, Jones GL, Cheeks JP.Twelve clinically sound, healthy, athletically conditioned Thoroughbred horses were subjected to an incremental exercise stress test to determine the effects and period of detection of a single dose of flunixin meglumine (1.1 mg/kg by intravenous injection) in serum and urine by ELISA. Flunixin concentrations, performance, and hematologic and clinical chemical parameters were measured. All horses were rotated through four treatment groups of a Latin-square design providing for each horse to serve as its own control. Flunixin meglumine reduced prostaglandin F(1alpha) and thromboxane concentrati...
Moslemi S, Seralini GE.In order to approach the detailed structure-function relationships of aromatase, we studied the inhibitory and inactivatory potencies of several steroidal androstenedione analogues (1: 4-hydroxyandrostenedione, 2: 4-acetoxyandrostenedione and 3: 7 alpha-(4'-amino)phenylthio-4-androstene-3, 17-dione) and non-steroidal imidazole derivatives (4: ketoconazole, 5: miconazole and 6: fadrozole) on equine aromatase in placental microsomes, a well established mammalian model. Human placental microsomes and the purified enzyme from equine testis were also used to compare inhibition by 1 and 2. In equine...
Feige K, Dennler M, Kästner SB, Wunderli-Allenspach H, Demuth D, Huber A.Recombinant (r)-hirudin is a specific inhibitor of thrombin that is independent of the activity of antithrombin. Objective: To evaluate pharmacokinetic properties and coagulatory changes of r-hirudin in healthy horses. Methods: Two clinically healthy horses received a single i.v. bolus of 0.4 mg/kg bwt r-hirudin and 6 clinically healthy horses received the same dose subcutaneously (subcut.) q. 12 h for 3 days. Coagulation times and r-hirudin plasma concentration were determined over 720 mins and 3 days after i.v. and subcut. administration, respectively. Results: In all horses, treatment with ...
Vieitez V, Gómez de Segura IÁ, Martin-Cuervo M, Gracia LA, Ezquerra LJ.Lipid emulsion has been reported to be effective for the treatment of local anaesthetic overdoses in rats, dogs and man. Objective: To describe the successful treatment of cardiovascular lidocaine toxicity in a foal with intravenous lipid administration. Methods: Observational study: case report. Methods: An 8-month-old Arabian cross foal was anaesthetised for removal of the right alar fold and nasal plate. Anaesthesia was maintained with isoflurane in oxygen and lidocaine administered with a loading dose followed by a continuous rate infusion (CRI). The anaesthetic period was uneventful and 3...
Puigdemont A, Ramis J, Guitart R, Arboix M.Usually, smaller mammals have higher clearances per unit body mass than do larger mammalian species. When clearance and other pharmacokinetic parameters are correlated with internal physiological processes, species tend to dispose of drugs at a similar pace. The first application of this concept is pharmacokinetic time, expressed with different units: Kallynochron, Apolysichron, Dienetichron, and Syndesichron. The present work describes pharmacokinetic time in these units from data obtained with propafenone in eight animal species: mouse, rat, rabbit, dog, sheep, human, cow, and horse. Additio...
Yokota S, Hikasa Y, Shimura I, Kusunose S.To investigate effects of various imidazoline and nonimidazoline α-adrenergic agents on aggregation and antiaggregation of bovine and equine platelets. Methods: Blood samples obtained from 8 healthy adult cattle and 16 healthy adult Thoroughbreds. Methods: Aggregation and antiaggregation effects of various imidazoline and nonimidazoline α-adrenergic agents on bovine and equine platelets were determined via a turbidimetric method. Collagen and ADP were used to initiate aggregation. Results: Adrenaline, noradrenaline, or α-adrenoceptor agents alone did not induce changes in aggregation of bov...
Her GR, Watson JT.Sensitive and specific methodology based on capillary column gas chromatography-electron capture-negative chemical ionization-mass spectrometry has been developed for the quantitative analysis of corticosteroids from biological fluids. The feasibility of this method is demonstrated in the quantitative analysis of dexamethasone in horse urine following administration of the drug. A structurally similar compound, 6 alpha-methylprednisolone, is added to the urine as an internal standard. The free dexamethasone and the internal standard are extracted and oxidized to high-electron-affinity 1,4-andr...
Kilcoyne I, Nieto JE, Knych HK, Dechant JE.OBJECTIVE To determine the maximum concentration (Cmax) of amikacin and time to Cmax (Tmax) in the distal interphalangeal (DIP) joint in horses after IV regional limb perfusion (IVRLP) by use of the cephalic vein. ANIMALS 9 adult horses. PROCEDURES Horses were sedated and restrained in a standing position and then subjected to IVRLP (2 g of amikacin sulfate diluted to 60 mL with saline [0.9% NaCl] solution) by use of the cephalic vein. A pneumatic tourniquet was placed 10 cm proximal to the accessory carpal bone. Perfusate was instilled with a peristaltic pump over a 3-minute period. Synovial ...
Younkin JT, Santschi EM, Kukanich B, Lubbers BV, Warner M.Penicillin is administered intravenously (IV) or intramuscularly (IM) to horses for the prevention and treatment of infections, and both routes have disadvantages. To minimize these shortcomings, a 24-hr hybrid administration protocol (HPP) was developed. Our objective was to determine penicillin plasma concentrations in horses administered via HPP. Venous blood was collected from seven healthy horses administered IV potassium penicillin G at 0 and 6 hr and IM procaine penicillin G at 12 hr. Blood was collected at 2-hr intervals from 0 to 20 hr and at 24 hr. Plasma penicillin concentration...
Harkins JD, Dirikolu L, Lehner AF, Hughes C, Schroedter D, Mayer B, Bratton C, Fisher MV, Tobin T.Guanabenz (2,6-dichlorobenzylidene-amino-guanidine) is a centrally acting antihypertensive drug whose mechanism of action is via alpha2 adrenoceptors or, more likely, imidazoline receptors. Guanabenz is marketed as an antihypertensive agent in human medicine (Wytensin tablets, Wyeth Pharmaceuticals). Guanabenz has reportedly been administered to racing horses and is classified by the Association of Racing Commissioners International as a class 3 foreign substance. As such, its identification in a postrace sample may result in significant sanctions against the trainer of the horse. The present ...
Queiroz-Neto A, Zamur G, Carregaro AB, Mataqueiro MI, Salvadori MC, Azevedo CP, Harkins JD, Tobin T.Caffeine is the legal stimulant consumed most extensively by the human world population and may be found eventually in the urine and/or blood of race horses. The fact that caffeine is in foods led us to determine the highest no-effect dose (HNED) of caffeine on the spontaneous locomotor activity of horses and then to quantify this substance in urine until it disappeared. We built two behavioural stalls equipped with juxtaposed photoelectric sensors that emit infrared beams that divide the stall into nine sectors in a 'tic-tac-toe' fashion. Each time a beam was interrupted by a leg of the horse...
Current drug metabolismDecember 19, 2020
Volume 22, Issue 3 215-223 doi: 10.2174/1389200221666201217141025
Hu SX, Ernst K, Benner CP, Feenstra KL.Pharmacokinetic and pharmacodynamic assessment of ester-containing drugs can be impacted by hydrolysis of the drugs in plasma samples post blood collection. The impact is different in the plasma of different species. Objective: This study evaluated the stability of a prodrug, ketoprofen methylester (KME), in commercially purchased and freshly collected plasma of mouse, rat, dog, cat, pig, sheep, cattle and horse. Methods: KME hydrolysis was determined following its incubation in commercially purchased and freshly collected plasma of those species. Different esterase inhibitors were evaluated f...
Landuyt J, Delbeke FT, Debackere M.The plasma concentrations of phenylbutazone (PBZ) and its major metabolites, oxyphenbutazone (OPBZ) and gamma-OH-phenylbutazone (OHPBZ) were determined for up to 72 h in six horses, following intravenous (i.v.) and intramuscular (i.m.) administration of 4 g phenylbutazone, 20 ml Phenylarthrite Ventoquinol (Vetoquinol Spécialités Pharmaceutiques Vétérinaires, Magny-Vernois, 70200 Lure, France). After i.v. dosing the plasma disposition was best described by a two-compartment open model. The hydroxylated metabolites OPBZ and OHPBZ were present in detectable concentrations for 72 h and 48 h, r...
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...
Matthews NS, Gleed RD, Short CE, Burrows K.Isoxsuprine (0.6 mg/kg) administered IV to 6 standing horses produced substantial, transient decreases in systemic blood pressure, systemic vascular resistance, and stroke volume. It also produced substantial, transient increases in heart rate, cardiac output, and purposeful movement. Plasma concentrations of isoxsuprine peaked soon after the drug was administered IV and then decreased over a 12-hour period in a biexponential manner, with distribution and elimination half-lives of 14 minutes and 2.67 hours, respectively. Total body clearance and steady-state volume of distribution were calcula...
