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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.
Immunoaffinity chromatography combined with gas chromatography-negative ion chemical ionisation mass spectrometry for the confirmation of flumethasone abuse in the equine. Immunoaffinity chromatography using a synthesised immunosorbent was used to extract tritiated dexamethasone (with dexamethasone carrier) from equine urine at a recovery of 81.7 +/- 8.4% (mean +/- S.D.). A method utilising this procedure coupled to cool on-column injection gas chromatography-negative ion chemical ionisation mass spectrometry is also described for the confirmation of low levels of flumethasone in equine urine samples.
Pharmacokinetics of cefotaxime in neonatal pony foals. Serum concentrations of cefotaxime and desacetylcefotaxime were measured in 1-week-old pony foals after IV administration of a single dose of cefotaxime. The cefotaxime disposition data conformed to a two-compartment model with elimination half-life of 0.60 hour. The combined cefotaxime and desacetylcefotaxime data was best described by a four-compartment model. The apparent half-life describing the disappearance of desacetylcefotaxime was 1.69 hours. Dosage of 40 mg/kg of body weight given IV every 4 to 6 hours for neonatal foals with gram-negative septicemia and every 2 hours for foals with ...
[Pain prevention and pain treatment in small and large domestic animals]. The aim of this article is to emphasize the need for analgesic medication in animals in possibly painful situations, especially in the postoperative period. The two large groups of compounds used as analgesics--the opiates and the nonsteroidal antiinflammatory drugs (NSAIDs)--are described with special reference to their pharmacokinetics, side-effects and toxicity, their mechanism of action, their indications and contraindications. Recommended doses of the different drugs available are given for the dog, the cat, the horse, the swine and the small and large ruminants.
Pharmacokinetics and concentrations of ceftiofur sodium in body fluids and endometrium after repeated intramuscular injections in mares. Each of 5 healthy mares was given 5 consecutive IM injections of ceftiofur sodium (2 mg/kg of body weight; 50 mg/ml) at 12-hour intervals. Ceftiofur concentrations were measured serially in serum, synovial fluid, peritoneal fluid, and urine, and were measured in CSF and endometrial tissue after the fifth dose. Mean elimination rate constant was 0.354 +/- 0.101 h-1 and elimination half-life was 2.49 +/- 0.49 hour. Mean serum ceftiofur concentrations peaked approximately 1 hour after each injection. The highest mean ceftiofur concentration was 5.09 micrograms/ml at 1 hour after the fifth dose fo...
Pharmacokinetic disposition of intravenous and oral pentoxifylline in horses. The pharmacokinetics of pentoxifylline (P) and its alcohol metabolite I (MI) were determined after administration of intravenous pentoxifylline, sustained release pentoxifylline tablets (Trental), and crushed pentoxifylline tablets in corn syrup, to five healthy adult horses. Pharmacokinetics were evaluated in a model-independent manner. After intravenous administration, pentoxifylline was rapidly eliminated (mean residence time 1.09 +/- 0.67 h), had a large steady-state volume of distribution (2.81 +/- 1.16 l/kg), and high clearance (3.06 +/- 1.05 l/kg/h). Oral absorption of pentoxifylline fr...
Pharmacokinetics and applications of ampicillin sodium as an intravenous infusion in the horse. A regime for administration of ampicillin sodium by continuous intravenous infusions to horses was designed. The aim was to achieve plasma ampicillin concentrations between 5 and 10 micrograms/ml over a 4-h period. A 2 mg/kg bodyweight loading dose of ampicillin sodium was administered intravenously at the beginning of the infusion in order to achieve steady-state plasma concentrations rapidly. The infusion system subsequently administered ampicillin at a rate of approximately 19.2 micrograms/min/kg bodyweight. The plasma concentrations obtained over the infusion period correlated very well wi...
Pharmacokinetic profile of sulphamonomethoxine-trimethoprim in horses after intravenous, intramuscular and oral administration. The pharmacokinetic profile of a sulphamonomethoxine-trimethoprim (SMM-TMP) combination was investigated in five horses. The combination was administered intravenously, intramuscularly and orally at a constant dose of 20 mg SMM plus 4 mg TMP kg-1 bodyweight. Following intravenous administration both drugs dispersed rapidly with distribution half-lives of about 12 minutes for SMM and about 18 minutes for TMP. Elimination half-lives for intravenous, intramuscular and oral administration were closely similar, indicating that elimination was independent of administration route. Bioavailability of ...
[Comparative enantioselectivity of the disposition of two non-steroidal anti-inflammatory agents, ketoprofen and carprofen, in man and animals]. After the administration of racemic ketoprofen and carprofen to man, both enantiomers of each compound exhibit similar plasma profiles. This contrasts with the rat where the active S(+) enantiomer is predominant. For carprofen, regardless of the route of administration, the R(-) enantiomer is predominant in the plasma of all investigated animal species. The S(+)/R(-) ratio of the "areas under the curves" during the time course of the kinetics, is: 0.60 in dogs, 0.53 in Yucatan micro-pigs, 0.48 in mini-goats, 0.67 in calves and 0.19 in horses. For ketoprofen, the S(+) enantiomer is predominant ...
Serum concentrations of ormetoprim/sulphadimethoxine in 1-3-day-old foals after a single dose of oral paste combination. Ormetoprim (OMP)/sulphadimethoxine (SDM) combinations
have been used in the treatment of fowl cholera, colibacillosis,
salmonellosis, infectious coryza, and other bacterial infections in
poultry (Mitrovic et al. 1969; Maestrone et al. 1979). The drug
combination has also been used in the treatment of colibacillosis
in neonatal pigs (Brandt and Maestrone 1980) and Pasteurella
pneumonia in cattle (Ames et al. 1987). Serum concentrations and
pharmacokinetics of SDM (Oh-Ishi and Nakajima 1964; Durr et
al. 1980) and OMP/SDM (Brown et al. 1989) after intravenous or
oral administration to ad...
Closed-circuit liquid injection isoflurane anesthesia in the horse. Six horses were administered isoflurane anesthesia by liquid injection into a closed breathing circuit according to the square root of time model. The unit dose (UD) was calculated using Lowe's formula to provide an end-tidal concentration of 1.3%, or the minimum alveolar concentration of isoflurane. The mean UD was 4.2 +/- 0.2 mL. The mean end-tidal isoflurane concentration (ETiso) for each interval after injection, and the peak and minimum concentrations for each injection interval, did not change beginning with the second injection, indicating that the square root of time model accurately p...
Kinetic analysis of D-xylose distribution after intravenous administration to mares. Multicompartmental analysis was applied to study the kinetics of D-xylose distribution after IV administration to healthy mares deprived of food for 12 and 96 hours. Urinary excretion of D-xylose was measured over a 15-hour period after administration. The plasma D-xylose concentrations in this study were in the range found after oral tolerance testing. The disposition of D-xylose was described by a two-compartment model with linear kinetic characteristics. Total volume of distribution decreased significantly (P < 0.025) from 0.270 L/kg of body weight after the 12-hour period of food depriv...
Kinetics and pharmacology of estrogens in pre- and postmenopausal women. With the approach of the menopause and the cessation of ovarian estrogen production, a number of uncomfortable and/or dangerous conditions may be manifested, and are all indications for estrogen replacement therapy. Various routes of estrogen administration are available--oral, subcutaneous implant, intravaginal, and transdermal--each having advantages and disadvantages. There is also a choice possible among replacement hormones, which include the natural estrogens, such as estradiol and estropipate; synthetic estrogens, for example, ethinyl estradiol and diethylstilbestrol; and conjugated equ...
Vancomycin kinetics in plasma and synovial fluid following intravenous administration in horses. Vancomycin hydrochloride was infused intravenously (i.v.) over a 30-min period in five horses at doses of 6.6, 11.0 and 15.4 mg/kg. Vancomycin concentration in plasma and synovial fluid samples was measured using a polarization immunoassay. A pharmacokinetic model was developed to accommodate the special features of the present study. The data were described by a two compartment open model with synovial fluid as an additional compartment in exchange with plasma. Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were measured for Staphylococcus aureus and Enteroco...
Identification of a benzhydrolic metabolite of ketoprofen in horses by gas chromatography-mass spectrometry and high-performance liquid chromatography. A benzhydrolic metabolite of ketoprofen, formed by reduction of the keto group of the drug, has been identified by gas chromatography-mass spectrometry in equine plasma and urine. After partial synthesis, its structure has been confirmed by UV, IR and 1H NMR spectroscopy. The kinetics of ketoprofen and this metabolite have been monitored in plasma by high-performance liquid chromatography. The two products were quantified in plasma up to 4 and 3 h, respectively, and were detected in urine up to 72 and 24 h, respectively, after a single intravenous administration to horses at the dose of 2.2 mg...
Pharmacokinetics of intravenously and orally administered pyrimethamine in horses. Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered IV and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The IV and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after IV administration was 1,521 ml/kg and the...
Distribution studies of theophylline: microdialysis in rat and horse and whole body autoradiography in rat. After intravenous administration of theophylline, microdialysis has been used for studying the non protein bound theophylline concentration in blood and in lung tissue in the rat as well as in two horses. The distribution pattern of 14C-theophylline in the rat was also investigated. When the distribution of theophylline was completed the time course of free drug in the interstitial fluid in lung tissue was in good agreement with the total concentration-time profile in plasma in both species. In the rat the free concentration of theophylline in the lung was slightly lower than the free concentr...
Pharmacokinetics, penetration into cerebrospinal fluid, and hematologic effects after multiple oral administrations of pyrimethamine to horses. Pharmacokinetics, CSF penetration, and hematologic effects of oral administration of pyrimethamine were studied after multiple dosing. Pyrimethamine (1 mg/kg of body weight) was administered orally once a day for 10 days to 5 adult horses, and blood samples were collected frequently after the first, fifth, and tenth doses. The CSF samples were obtained by cisternal puncture 4 to 6 hours after administration of the first, third, seventh, and tenth doses. Pyrimethamine concentration in plasma and CSF was quantified by gas chromatography, and plasma concentration-time data were analyzed, using a ...
Adverse drug reactions: report of the Australian Veterinary Association Adverse Drug Reaction Subcommittee, 1992. Fifty-nine reports of suspected adverse drug reactions (ADRs) were received by the Adverse Drug Reaction Subcommittee of the Australian Veterinary Association from February 1991-March 1992 inclusive. The number of reports received/number of animals involved per species was: dogs (23/24); cats (20/30); horses (4/4); cattle (7/10); sheep (3/745); poultry (1/580); pigs (1/8). Of these, 38 (64%) were classified as definite ADRs and 9 (15%) as probable ADRs. In 10 (17%) reports an ADR could not be substantiated or there was insufficient information available to make a decision. Two reports involved...
Safety of ceftiofur sodium administered intramuscularly in horses. Ceftiofur sodium, a broad-spectrum cephalosporin antibiotic, was evaluated for safe use in horses. Male or female horses were allotted to groups and were given either saline solution (control), or 2.2, 6.6, or 11 mg of an aqueous solution of ceftiofur sodium/kg of body weight/d, IM, for 30 or 31 days. These dosages are expressed in terms of the ceftiofur free acid, and represent 1 to 5 times the proposed therapeutic dosage (2.2 mg/kg/d) administered for 3 times the maximal recommended duration of 10 days. Some of the horses were euthanatized and necropsied on day 31 or 32. The other horses wer...
Effects of hypoxia and azotaemia on the pharmacokinetics of amikacin in neonatal foals. The effects of hypoxia and azotaemia on the pharmacokinetics of amikacin were evaluated in 20 full-term neonatal critically ill foals which required 24-h supportive care, antibiotics and dextrose-supplemented polyionic fluids given intravenously, nasal insufflation with oxygen and nutritional supplementation. There was no association between sepsis score or survival and pharmacokinetic parameters. Concurrent hypoxia and azotaemia were associated with significantly decreased clearance and increased peak and trough serum concentrations of amikacin; however, peaks or troughs did not exceed toxic ...
Acetylsalicylic acid and blood coagulation in the horse. Equine blood may contain salicylic acid (SA) taken up as free acid or represents the metabolite of acetylsalicylic acid (ASA). To obtain information of SA in race horses we screened blood samples of trotting-horses routinely drawn to be analyzed for doping substances. The individual values determined followed a Gaussian distribution displaying a geometric mean of 19 ng SA per ml serum. A probit analysis revealed linear relationship (r = 0.995). Additional studies examined the antithrombotic efficacy of ASA in the horse. An oral dose of 300 mg ASA considerably elevated the bleeding time for mor...
Pharmacokinetics of metronidazole and its concentration in body fluids and endometrial tissues of mares. Serum concentrations of metronidazole were determined in 6 healthy adult mares after a single IV injection of metronidazole (15 mg/kg of body weight). The mean elimination rate (K) was 0.23 h-1, and the mean elimination half-life (t1/2) was 3.1 hours. The apparent volume of distribution at steady state was 0.69 L/kg, and the clearance was 168 ml/h/kg. Each mare was then given a loading dose (15 mg/kg) of metronidazole at time 0, followed by 4 maintenance doses (7.5 mg/kg, q 6 h) by nasogastric tube. Metronidazole concentrations were measured in serial samples of serum, synovia, peritoneal flui...
Effects of ketamine infusion on halothane minimal alveolar concentration in horses. Eight adult horses were used in a study to determine ketamine's ability to reduce halothane requirement. To obtain steady-state plasma concentrations of 0.5, 1.0, 2.0, 4.0, and 8.0 micrograms/ml, loading doses and constant infusions for ketamine were calculated for each horse on the basis of data from other studies in which the pharmacokinetic properties of ketamine were investigated. Blood samples for determination of plasma ketamine concentrations were collected periodically during each experiment. Plasma ketamine concentrations were determined by capillary gas chromatography/mass spectromet...
