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.
Use of phenytoin to treat horses with Australian stringhalt. Five horses with Australian stringhalt were treated with 15 mg/kg phenytoin orally for 2 weeks. During the second week of the trial, 3 of the horses were given an additional dose of 10 mg/kg phenytoin. The response to treatment was clinically assessed by grading the severity of the gait abnormality at the walk, trot, turning and backing twice daily. There was a significant (P less than 0.05) improvement in the gait abnormality when pre-treatment values were compared with the mean of the last 3 assessments before treatment stopped. When reassessed 2 weeks after treatment ceased, there remained ...
Eltenac, a new anti-inflammatory and analgesic drug for horses: clinical aspects. Two controlled studies to determine efficacy in the horse were performed with eltenac, a new injectable, non-steroidal anti-inflammatory drug (NSAID). Clinical trials were carried out with a dose rate of 1 mg/kg body weight in a randomized, placebo-controlled, double-blind design to assess therapeutic efficacy in acute inflammatory disorders and in animals with orthopaedic conditions. In a preliminary pharmacokinetic investigation in six horses mean elimination half-life was 1.7 h after i.v. administration. In the first clinical study, analgesic activity on pain-related lameness was determined...
Evaluation of the oral vitamin E absorption test in horses. An oral vitamin E absorption test used in human beings was modified for use in horses. The most appropriate techniques with which to measure gastrointestinal tract absorption of vitamin E (alpha-tocopherol) in horses were developed. Vitamin E was administered orally, and serum values of alpha-tocopherol were measured by use of high-performance liquid chromatography at 0, 3, 6, 9, 12, and 24 hours after vitamin E administration. Variables included comparison of 2 dosages (45 and 90 IU/kg of body weight), routes of administration, and absorption dynamics of 3 preparations of dl-alpha-tocopherol....
Disposition of human drug preparations in the horse. I. Rectally administered indomethacin. A high-performance liquid chromatographic method to measure urinary indomethacin levels is described. In 0.5 ml urine, 1 micrograms/ml of indomethacin could be detected. Alkaline hydrolysis of urine resulted in the decomposition of indomethacin. When two suppositories of Indocid corresponding to 200 mg indomethacin were administered rectally to four horses the drug was rapidly absorbed and remained detectable in urine from 1 to 12 h. The excretion rate peaked after 2-3 h while the maximal concentration ranged from 18.5 to 80.6 micrograms/ml. Only 8 to 16% of the indomethacin dose was eliminate...
Pharmacodynamics and pharmacokinetics of miloxicam in the horse. The novel non-steroidal anti-inflammatory drug (NSAID) miloxicam was administered intravenously to six New Forest ponies at a dosage rate of 0.6 mg/kg in a two-part cross-over study. In each part, three horses received miloxicam and three were given a placebo preparation. The actions of miloxicam, compared to placebo, were assessed in a carrageenan-sponge model of acute inflammation. The rise in skin temperature over the site of the acute inflammatory reaction was less in treated ponies, but differences were not statistically significant. Concentrations of the enzymes acid phosphatase (AP) and...
Pharmacokinetics and bioavailability of ticarcillin and clavulanate in foals after intravenous and intramuscular administration. The pharmacokinetics and bioavailability of ticarcillin and clavulanate were determined after intravenous (i.v.) or intramuscular (i.m.) administration of ticarcillin disodium (50 mg/kg) combined with clavulanate potassium (1.67 mg/kg) to groups of healthy foals at 3 days and 28 days of age. After i.v. administration of the combination to five foals, the disposition kinetics of ticarcillin and clavulanate were best described using a two-compartment open model. Mean plasma elimination-rate constant (beta) and clearance (ClB) for ticarcillin were significantly less (P less than 0.01), and volume...
Ototoxic potential of gentamicin in ponies. Ototoxicosis was evaluated in 6 healthy ponies given 5 mg of gentamicin/kg of body weight, q 8 h, IM. Ponies 1, 2, and 3 were dosed for 7 days and ponies 4, 5, and 6 were dosed for 14 days. Serum peak and trough concentrations of gentamicin were measured by radioimmunoassay at regular intervals. Brain stem auditory-evoked responses were recorded every 5 days up to 60 days after the first dose to monitor auditory function. Although serum gentamicin concentrations were within or above the accepted clinical therapeutic range, loss of auditory function was not observed at the frequency range (1 to...
Urinary excretion of theobromine in horses given contaminated pelleted food. A high pressure liquid chromatographic (HPLC) method for measuring the theobromine content in cocoa husks, pelleted food and horse urine is described. Starting with 2 ml of urine, concentrations of 500 ng/ml could easily be detected. When feed containing 38.4 mg of theobromine was given twice daily to horses for 2 1/2 days, two days were needed after the last intake before the theobromine concentrations fell below the threshold value of 2 micrograms/ml. The time at which the peak excretion rate occurred varied from 2 to 12 h after the last administration, while the excretion rate seemed to be ...
Characterization of bromhexine and ambroxol in equine urine: effect of furosemide on identification and confirmation. The purpose of this study was two-fold: (1) to develop a simple and sensitive screening procedure for identifying and confirming bromhexine and ambroxol and, (2) to determine the effect of furosemide on the detection of bromhexine, ambroxol, or their metabolites in urine. Female horses (450-550 kg) treated with bromhexine or ambroxol (1 g, p.o.) were used. Urine samples were collected up to 48 h post-drug administration and analysed. Blind samples were used in evaluating the sensitivity of these methods and reproducibility of the results. Bromhexine and ambroxol were extensively metabolized in...
Chloramphenicol 3. Clinical pharmacology of systemic use in the horse. The use of chloramphenicol in the horse is now prohibited as horses are classified as food-producing animals. However, chloramphenicol has until recently been widely available for oral, intramuscular or intravenous administration. A critical appraisal of the published literature on the use of chloramphenicol in the horse clearly demonstrates that there are sound pharmacokinetic and microbiological reasons for concluding that chloramphenicol is not an appropriate antibiotic for systemic use. The short half-life of chloramphenicol in the horse, together with the broad range of minimum inhibitory...
Effect of interval between doses on response of the pony to sodium bicarbonate. Three pony geldings were given sodium bicarbonate orally in order to study the effect on blood pH and bicarbonate and to determine if frequency of dosing influences the response. In a preliminary study, it appeared that a carry-over effect might occur if the interval between dosing was only 2 days. The ponies received 2 doses of sodium bicarbonate (400 mg/kg) 7 days apart in trial one and then in trial two they received 2 doses of sodium bicarbonate 4 days apart. The sodium bicarbonate was mixed with 2 liters of warm water and given through a nasogastric tube on each trial day. Blood samples w...
Low dose calcium heparin in horses: plasma heparin concentrations, effects on red blood cell mass and on coagulation variables. Low dose calcium heparin was administered subcutaneously at 12 hourly intervals to six healthy horses at an initial dose of 150 iu of heparin/kg bodyweight (bwt) and at a maintenance dose of 120 iu/kg bwt. All injections were given at 0900 and 2100 h. Blood samples for monitoring plasma heparin concentrations were obtained prior to, at 2 hourly intervals for 84 h (treatment period), and at Hours 24, 32, 48 and 96 of the control period. Blood samples for monitoring red blood cell (RBC) mass, plasma antithrombin III activity (AT III), activated partial thromboplastin time (APTT), and thrombin ti...
Clinical signs, laboratory changes and toxicokinetics of brodifacoum in the horse. Six horses gavaged with a commercial brodifacoum (BDF)-containing bait (Talone) at a dosage of 0.125 mg of BDF/kg of body weight showed weight loss, severe hypocoagulability and hemogram alterations. Four of the horses became depressed and anorectic; one required vitamin K1 therapy. Increases in clotting times were observed at 24 h in the partial thromboplastin time (PTT) followed by the thrombotest (TBT) and one-stage prothrombin time (PT) at 48 h. Elevated mean PTT, PT and TBT were observed from days 4 to 8 (p less than 0.05) with levels returning to pretreatment levels by day 12. Maximum pr...
Treatment of atrial fibrillation in horses by intravenous administration of quinidine. Intravenous administration of quinidine gluconate converted atrial fibrillation (AF) to sinus rhythm in 9 of 12 horses. Twelve horses that were diagnosed by ECG to have AF were administered up to 11 mg of quinidine gluconate/kg of body weight in 1.0- to 1.5-mg/kg bolus injections every 10 to 15 minutes. The total dose of quinidine administered IV ranged from 1.8 to 5.8 g. Increased ventricular rate, apprehension, and mild depression were observed during treatment. Other signs of toxicosis were not observed. One horse was successfully treated with IV administered quinidine gluconate on 3 occasi...
Prolongation of anesthesia with xylazine, ketamine, and guaifenesin in horses: 64 cases (1986-1989). On 74 occasions, 54 horses and 6 foals were anesthetized with xylazine and ketamine or xylazine, guaifenesin, and ketamine, with or without butorphanol. On 64 occasions, anesthesia was prolonged for up to 70 minutes (34 +/- 15 min) by administration of 1 to 9 supplemental IV injections of xylazine and ketamine at approximately a third the initial dosage. All horses except 5 were positioned in lateral recumbency, and oxygen was insufflated. In adult horses, the time from induction of anesthesia to the first supplemental xylazine and ketamine injection was 13 +/- 4 minutes and the time between s...
[Detection of dexamethasone in horses]. Due to their marked antiinflammatory effect, synthetic corticosteroids are used to mask illness, especially lameness in horses. The detection of these drugs in equine body fluids requires accurate methods, particularly where misuse of corticosteroids is suspected. Gas chromatography/mass spectrometry (GC/MS) is well established as a reliable technique for the identification of drugs in biological fluids. Using GC/MS, we determined dexamethasone levels in horse urine and serum after intravenous application of a therapeutic dose. Dexamethasone was detectable, in serum for up to six hours, and in...
Use of halothane and isoflurane in the horse. When compared with halothane, isoflurane has several distinct characteristics. Vaporizer settings are higher because of its lower potency. Respiratory rates will be slower, and intraoperative changes in depth and recovery from surgical depth of anesthesia will be more rapid, although total recovery times frequently will not be different. Halothane and isoflurane appear similar in their effects on ocular reflexes and mean arterial blood pressure. Recovery from isoflurane should be managed to provide added sedation or physical support if the horse attempts to stand prematurely.
Neuromuscular blocking agents in equine anesthesia. In summary, neuromuscular blocking agents can be used safely and to advantage in equine anesthesia. Muscle-relaxant use in equine anesthesia has been helped by the development of new relaxants such as atracurium, which has a reliable and reproducible duration of action. There are certain cases that benefit particularly by the use of relaxants but their use is not limited to these cases. These cases involve horses that experience persistent movement and hypotension during anesthesia, are undergoing ophthalmic or abdominal surgery or fracture repair, or are severely ill. Horses receiving muscle ...
Chemical restraint and analgesia in the horse. Chemical restraint in the standing horse is used for a variety of procedures in veterinary medicine. The choice of agent depends on the physical status, temperament, and size of the patient; the procedure to be performed; and safety for the patient, veterinarian, and owner. The combination of certain agents may provide more desirable restraint and analgesia than does the use of individual agents. The use of analgesics in the horse is not without side effects, some of which may be detrimental to the patient's condition. Analgesics should be chosen with these untoward effects in mind. Draft bree...
Pharmacokinetics of gentamicin in newborn to 30-day-old foals. Gentamicin sulfate, equivalent to 4 mg of gentamicin base/kg of body weight, was administered IV to 6 Thoroughbred foals on day 1 (12 to 24 hours of age) and at 5, 10, 15, and 30 days after birth. On day 40 after parturition, gentamicin was given to the mares at a dosage similar to that used in foals. Decay of serum gentamicin concentrations was best described by a 2-compartment model. Among foals, the overall elimination rate constant at 30 days of age was significantly (P less than 0.05) greater than at days 1, 10, and 15. There was, however, no difference in the overall elimination rate con...
Bioavailability of ascorbic acid in horses. The bioavailability of ascorbic acid administered to thoroughbreds by intramuscular injection was investigated. For intramuscular injection two preparations were studied, and the percentage bioavailability up to 24 h of 10 g of ascorbic acid was 95% +/- 22 in four horses and 60% in two horses with preparations A and B, respectively. Bioavailability at 24 h in three horses injected subcutaneously with 10 g of preparation B was 82%. Intramuscular injection of both preparations was apparently well tolerated while subcutaneous injection of preparation B (pH 6.0) was associated with marked irritanc...
Hordenine: pharmacology, pharmacokinetics and behavioural effects in the horse. Hordenine is an alkaloid occurring naturally in grains, sprouting barley, and certain grasses. It is occasionally found in post race urine samples, and therefore we investigated its pharmacological actions in the horse. Hordenine (2.0 mg/kg bodyweight [bwt]) was administered by rapid intravenous (iv) injection to 10 horses. Typically, dosed horses showed a flehmen response and defecated within 60 secs. All horses showed substantial respiratory distress. Respiratory rates increased about 250 per cent and heart rates were approximately double that of resting values. All animals broke out in a sw...
Prophylactic use of dantrolene associated with prolonged postanesthetic recumbency in a horse. Dantrolene, a drug used in the prevention and treatment of malignant hyperthermia, was believed responsible for prolonged postanesthetic recumbency in a horse. Prophylactically, dantrolene was given orally before induction of anesthesia. Dantrolene has been recommended for use in horses at risk of developing postanesthetic myopathy. Side effects, including ataxia, may result from dantrolene administration.
[The treatment basis for anticoagulants in horses]. The pharmacokinetics of racemic phenprocoumon were studied in 8 adult horses after the single intravenous and oral administration of 0.75 mg/kg. After i.v. administration the plasma concentration of phenprocoumon showed a biphasic decline in time. The pharmacokinetics were calculated on the two-compartment open model. The average plasma half-life (beta-phase) was 22 hours, the apparent volume of distribution was 0.61 l/kg, Cltot was 25.2 ml/kg/h (13.9-40.9 ml/kg/h). The systemic bioavailability of oral phenprocoumon was 97.6%, Tmax was found to be 4-12 hours. The effect of phenprocoumon on the...
Effect of antimicrobial solution lavage on the palmar digital tendon sheath in horses. Sixteen horses were allotted to 4 groups of 4 horses each to evaluate the effect of tendon sheath lavage with 4 solutions (balanced electrolyte solution, 0.1% povidone-iodine, 0.5% povidone-iodine, and 0.5% chlorhexidine). The synovitis caused by 0.1% povidone-iodine lavage was not appreciably worse than that caused by balanced electrolyte solution lavage, but the 0.5% povidone-iodine and chlorhexidine lavages caused severe synovitis, and, therefore, should not be used for tendon sheath lavage.