Topic:Pharmacokinetics
Pharmacokinetics in horses involves the study of how drugs are absorbed, distributed, metabolized, and excreted in equine species. This field of study provides insights into the time course of drug concentrations within the horse's body and helps in understanding the effects of various pharmaceuticals. Key parameters in equine pharmacokinetics include absorption rates, bioavailability, half-life, and clearance. These parameters can vary significantly due to factors such as age, breed, and health status of the horse. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacokinetic profiles of different drugs in horses, aiming to optimize dosing regimens and improve therapeutic outcomes in equine medicine.
Biotransformation of 1-dehydrotestosterone in the equine male castrate: identification of the neutral unconjugated and glucuronic acid conjugated metabolites in horse urine. The in vivo biotransformation of (1,2(n)-3H)1-dehydrotestosterone was studied in three equine male castrates and a number of neutral metabolites were identified in the urinary unconjugated and glucuronic acid conjugate fractions by gas chromatography/mass spectrometry. The metabolites were extracted from aliquots of the 0-24 h urine samples by Amberlite XAD-2 and separated into combined unconjugated plus glucuronic acid conjugated and sulphoconjugated fractions by Sephadex LH-20 column chromatography. After enzymatic hydrolysis of the glucuronides, the crude neutral unconjugated steroids plus ...
Hydrocortisone secretion: production rate and pulse characterization by numerical deconvolution. Based on serial blood sampling over 24 h, hydrocortisone was shown to be secreted episodically in the horse. The purpose of the present experiment was to characterize peaks and troughs by analyzing the instantaneous secretion rate profile obtained by a deconvolution technique rather than from the plasma concentration time profile. Kinetic parameters of hydrocortisone were determined following intravenous bolus and intravenous perfusion of hydrocortisone. Stationary and nonlinearity of hydrocortisone disposition were demonstrated. With the use of clearance values calculated from constant perfus...
Disposition and excretion of flunixin meglumine in horses. The disposition of flunixin meglumine administered IV at a dosage of 1.1 mg/kg was described by a 2-compartment model; the alpha and beta half-lives (t1/2) were 0.61 and 1.5 hours, respectively. When administered IV at a rate of 2.2 mg/kg, the disposition was best described by a 3-compartment model, and the alpha, beta, and lambda t1/2 were 0.16, 1.52, and 6.00 hours, respectively. The zero-time plasma concentrations after flunixin meglumine was administered at 1.1 and 2.2 mg/kg were 9.3 +/- 0.76 and 21.5 +/- 7.4 mg/L, respectively. The bioavailability after oral administration of 1.1 mg/kg wa...
Oxfendazole: activity of a two-dose treatment regimen on natural infections of internal parasites of equids, with emphasis on migrating large strongyles in controlled tests in 1986 and 1987. Oxfendazole paste formulation was administered intraorally at a dosage of 10 mg/kg of body weight, twice (48 hours between treatments) in 5 controlled tests (experiments A, B, C, D, and E) to 18 equids (14 horses and 4 ponies) that were 5 to 24 months old in 1986 and 1987. Activity was evaluated against naturally acquired infections of various internal parasites, with emphasis on migratory stages of Strongylus vulgaris and S edentatus. The number of treated and nontreated equids in each experiment (horses in experiments A to D and ponies in experiment E) was: A, 1 and 1; B, 3 and 3; C, 3 and 1...
Prednisolone binding to plasma proteins in domestic species. The binding of prednisolone to total plasma proteins of dogs, horses, cows, and sheep was characterized using equilibrium dialysis. Prednisolone was bound to a first protein with high affinity but low capacity (transcortin) and to a second protein according to a nonsaturable mechanism (albumin). Interspecies differences were observed, with cows and dogs exhibiting the lowest, and sheep and horses the highest specific binding capacities. The results are in good agreement with known pharmacokinetic properties of prednisolone in domestic species.
Serum and synovial fluid steady-state concentrations of trimethoprim and sulfadiazine in horses with experimentally induced infectious arthritis. The tarsocrural joints of 11 horses were inoculated with 1.2 to 2.16 x 10(6) viable Staphylococcus aureus organisms susceptible to a trimethoprim-sulfadiazine (TMP-SDZ) combination with minimal inhibitory concentration (MIC) of 0.25 micrograms of TMP/ml and 4.75 micrograms of SDZ/ml. Antimicrobial treatment consisted of oral administration of a TMP-SDZ combination--30 mg/kg of body weight given once daily (group-1 horses) or 60 mg/kg given as 30 mg/kg every 12 hours (group-2 horses). Paired serum and synovial fluid samples were obtained before intra-articular inoculation with the S aureus, aft...
Pharmacokinetics and estimated bioavailability of amoxicillin in mares after intravenous, intramuscular, and oral administration. The pharmacokinetics and estimated bioavailability of amoxicillin were determined after IV, intragastric, and IM administration to healthy mares. After IV administration of sodium amoxicillin (10 mg/kg of body weight), the disposition of the drug was best described by a 2-compartment open model. A rapid distribution phase was followed by a rapid elimination phase, with a mean +/- SD half-life of 39.4 +/- 3.57 minutes. The mean volume of distribution was 325 +/- 68.2 ml/kg, and the mean body clearance was 5.68 +/- 0.80 ml/min.kg. It was concluded that frequent IV administration of sodium amoxic...
Treatment of Fasciola hepatica infection in horses with triclabendazole. Thirteen thoroughbred foals with an adult infection and a presumed immature infection with Fasciola hepatica were treated with 12 mg triclabendazole/kg bodyweight. The absence of eggs from samples of faeces examined at intervals up to 110 days after treatment showed that all the animals were cured. In a second trial the same dose of triclabendazole cured 11 of 12 foals whereas nitroxynil at 7 mg/kg cured only six of 12 foals. No side effects were observed after treatment.
Combined use of detomidine with opiates in the horse. The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Sid...
In vitro evaluation of a sustained-release veterinary peroral pellet preparation. In a preceding in vivo study in horses, wide interindividual variation was found in the extent of bioavailability and time to reach peak concentration after peroral administration of one specific theophylline sustained-release dosage form. The purpose of the present study was to investigate the factors of potency, the pH of dissolution medium, the enzymes in the dissolution medium, and the crushing of the pellets on in vitro performance. The results show a wide variation in potency for the individual units, an increase in release rate with increasing pH, and an increase in release rate if the ...
Verification of ineffectual activity of ivermectin against adult Onchocerca spp in the ligamentum nuchae of horses. Ivermectin paste formulation (200 micrograms/kg) was administered orally to 27 horses (13 Thoroughbreds and 14 of mixed breeding) to evaluate activity against adult Onchocerca spp in the ligamentum nuchae. Ages, known or estimated, of the horses ranged from 1 to 22 years. Single or multiple doses (1 to 5) of the drug were given to each horse. When multiple doses were administered, the intervals between treatments ranged from 7 to 92 days. At 27 to 171 days after initial treatment (single dose or first of multiple doses), the horses were killed. Some of the horses treated more than once were ki...
Immunoassay detection of drugs in racing horses. VI. Detection of furosemide (Lasix) in equine blood by a one step ELISA and PCFIA. A one step enzyme-linked immunosorbent assay (ELISA) and a particle concentration fluorescent immunoassay (PCFIA) test for furosemide were evaluated as part of a panel of pre- and post-race tests for illegal medication of racing horses. These tests are very sensitive to furosemide with an I-50 for furosemide of about 20 ng/ml. The test is also rapid; an average pre-race complement of 10 samples can be analyzed in 90 minutes or less. The ELISA test results can be read with an inexpensive spectrophotometer, or even by eye. Both the PCFIA test and the ELISA test readily detect the presence of fur...
Species-dependent binding of disopyramide enantiomers. Serum protein binding of the basic enantiomers of disopyramide were studied in several animal species. (S)-(+)-Disopyramide was more highly bound than the (R)-(-)-enantiomer to serum protein in the man, gorilla, and pig. The reverse was true in cow serum, and in serum and albumin from sheep. Enantioselective differences in binding were due to differences in association constants. No enantioselective differences in binding were observed in serum protein from horse and goat, or in albumin from cow and pig. Disopyramide was highly bound to two sites on horse albumin. The association constant char...
Efficacy of ivermectin in the oral paste formulation against naturally acquired adult and larval stages of Parascaris equorum in pony foals. The efficacy of ivermectin in oral paste formulation at a dosage of 200 micrograms/kg of body weight was tested against naturally acquired larval and adult stages of Parascaris equorum, in a controlled study. Twenty infected pony foals 18 to 27 weeks of age were randomly allocated to 2 groups of 10 each and were placed in dry lots. Foals in 1 group were given ivermectin on day 0. Necropsies and parasite recoveries from small intestines and lung tissues were performed on 5 foals in each group at 2 weeks after treatment (WAT) and on the remaining foals at 5 WAT. Ivermectin was 100% effective aga...
Use of a narcotic antagonist (nalmefene) to suppress self-mutilative behavior in a stallion. Nalmefene, an opioid antagonist, caused a decrease in self-mutilative behavior in a 500-kg stallion. Self-mutilative attempts were counted during a control period and on 4 subsequent occasions after the IM administration of 100 mg, 200 mg, 400 mg, or 800 mg of nalmefene. The frequency of self-mutilation decreased with increasing doses of nalmefene and was virtually abolished with the 800-mg dose.
Development of a novel in vitro equine anthelmintic assay. An in vitro assay involving the use of a horse strongyle (Strongylus edentatus) and the micromotility meter has been developed to test for equine anthelmintic activity. Three commercially available equine anthelmintics (dichlorvos, ivermectin, and pyrantel pamoate) and an investigational drug (p-toluoyl chloride phenylhydrazone) were evaluated in this assay at four concentrations. After a 24-h incubation, greater than or equal to 10 micrograms/ml of all four drug treatments significantly (P less than or equal to 0.05) reduced the motility of ensheathed L-3 S. edentatus larvae, thereby indicati...
Pharmacokinetics and body fluid and endometrial concentrations of trimethoprim-sulfamethoxazole in mares. Six healthy adult mares were each given a single IV injection of trimethoprim (TMP)-sulfamethoxazole (SMZ) at a dosage of 2.5 mg of TMP/kg of body weight and 12.5 mg of SMZ/kg. Serum concentrations of each drug were measured serially over a 24-hour period. For TMP, the mean overall elimination rate constant (K) was 0.43/hr and the elimination half-life (t1/2) was 1.9 hours. The apparent volume of distribution (at steady state) was 1.62 L/kg and TMP clearance was 886 ml/hr/kg. For SMZ, K was 0.22/hr and t1/2 was 3.53 hours. The apparent volume of distribution at steady state was 0.33 L/kg and S...
Cardiovascular effects of hydralazine HCl administration in horses. Six standing awake adult horses were instrumented for measurement of mean arterial, central venous, and pulmonary arterial blood pressures (mm of Hg), thermodilution cardiac output (ml/kg/min), and pulmonary arterial blood temperature (C). Total peripheral resistance was calculated from these values. Base-line data were accumulated, and a single dose of hydralazine HCl (0.5 mg/kg) was administered IV. Horses were monitored for 420 minutes after hydralazine administration. Mean arterial and central venous blood pressures did not change from the base-line values. Cardiac output and heart rate we...
Radioimmunoassay for etorphine in horses with a 125I analog of etorphine. To improve the sensitivity and specificity of screening for etorphine in horses, an 125I-labeled etorphine analog was synthesized and an antibody to etorphine was raised in rabbits. A radioimmunoassay (RIA) for etorphine was developed, using these reagents. Bound and free 125I-labeled etorphine was separated by a double-antibody method that reduced interference from materials associated with equine urine. The 125I-labeled etorphine binding was rarely greater than 250 pg of background etorphine equivalents/ml in raw urine and was 100 pg/ml in hydrolyzed urine. The 125I-RIA was capable of detect...
Plasma and synovial fluid concentrations of gentamicin in horses after intra-articular administration of buffered and unbuffered gentamicin. The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater tha...
Comparative pharmacokinetics of yohimbine in steers, horses and dogs. In steers, horses and dogs, the comparative pharmacokinetics of yohimbine were determined using model-independent analysis. The intravenous dose of yohimbine was 0.25 mg/kg of body weight in steers, 0.075 or 0.15 mg/kg in horses, and 0.4 mg/kg in dogs. The mean residence time (+/- SD) of yohimbine was 86.7 +/- 46.2 min in steers, 106.2 +/- 72.1 to 118.7 +/- 35.0 min in horses, and 163.6 +/- 49.7 min in dogs. The mean apparent volume of distribution of yohimbine at steady state was 4.9 +/- 1.4 L/kg for steers, 2.7 +/- 1.0 to 4.6 +/- 1.9 L/kg for horses, and 4.5 +/- 1.8 L/kg for dogs. The total ...
Dose-dependent plasma elimination of subcutaneously administered calcium heparin in horses. Pharmacokinetic parameters for subcutaneous low dose heparin in horses have been determined. Four groups of five and one group of eleven mature, healthy horses of various breeds were given single subcutaneous injections of 60, 80, 100, 125, and 150 units of calcium heparin/kg of body weight (U/kg) in the pectoral region. Jugular blood samples were collected prior to, and at hourly intervals for 12 h after injection. Heparin plasma concentrations were measured using a commercially available amidolytic assay. Peak concentrations 4 h after administration were 0.021 +/- 0.016 (mean +/- SD) units o...