Topic:Biological Half-Life
Biological half-life refers to the time required for a substance to decrease by half in its concentration within the body. In horses, understanding the biological half-life of various substances, such as medications, nutrients, or toxins, is important for determining dosing schedules, withdrawal times, and potential effects on equine health. The biological half-life can vary significantly depending on the substance in question, as well as factors such as the horse's metabolism, age, and health status. This page compiles peer-reviewed research studies and scholarly articles that explore the biological half-life of different substances in horses, examining factors that influence these rates and their implications for veterinary medicine and equine management.
Bioavailability of oral penicillins in the horse: a comparison of pivampicillin and amoxicillin. 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...
Synovial and serum levels of triamcinolone following intra-articular administration of triamcinolone acetonide in the horse. Seven mature thoroughbred horses, weighing between 400 and 541 kg, were each injected intra-articularly into three joints with 6 mg/joint of triamcinolone acetonide (Vetalog). The fourth joint, the control, was injected with saline. Synovial fluid was taken from all four legs of the horses on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following the injections. Triamcinolone acetonide was assayed by a radioimmunoassay. Blood was collected at 1, 2, 4, 6, 12 h and on days 1, 2, 3, 4, 5, 6, 7, 8, 11, and 15 following injection of either triamcinolone or saline. Both cortisol and triamcinolone were as...
Plasma concentrations of flunixin in the horse: its relationship to thromboxane B2 production. The effects of the intravenous (i.v.) administration of 1.1 mg/kg of flunixin meglumine on thromboxane B2 (TxB2) concentrations were studied in sedentary and 2-year-old horses in training. The baseline TxB2 serum concentrations generated during clotting were 2.89 +/- 0.81, 2.19 +/- 0.25 and 0.88 +/- 0.12 ng/ml for the 2-year-old Thoroughbreds in training, sedentary horses under 10 and over 10 years old, respectively. There was a significant difference in baseline TxB2 concentrations between older and younger horses (P less than 0.005). Significant reduction in TxB2 production from baseline wer...
Effect of probenecid on disposition kinetics of ampicillin in horses. The effect of an oral dose of probenecid on the disposition kinetics of ampicillin was determined in four horses. An intravenous bolus dose (10 mg/kg) of ampicillin sodium was administered to the horses on two occasions. On the first occasion the antibiotic was administered on its own, and on the second occasion it was administered one hour after an oral dose of 75 mg/kg probenecid. The plasma concentration of probenecid reached a mean (+/- se) maximum concentration (Cmax) of 188-6 +/- 19.3 micrograms/ml after 120.0 +/- 21.2 minutes and concentrations greater than 15 micrograms/ml were present...
Bioavailability and bioequivalence of veterinary drug dosage forms, with particular reference to horses: an overview. The route of administration and formulation of the dosage form affect the bioavailability (rate and extent of absorption) of a drug and may thereby influence the intensity and duration of the pharmacological effect. Location of injection site may affect the plasma concentration profile of drugs administered as aqueous suspensions or sustained release parenteral preparations (procaine penicillin G). When absorption influences the rate of elimination ('flip-flop' phenomenon), the apparent half-life of the drug will be increased (cefazolin sodium, i.m.; meclofenamic acid, p.o.). Absorption genera...
Effect of changes in urine pH on plasma pharmacokinetic variables of ampicillin sodium in horses. The effect of urine pH on plasma disposition of ampicillin sodium was evaluated. A single dose of 10 mg/kg of body weight was administered IV to Thoroughbreds with alkaline (pH greater than 8.0) or acidic (pH less than 4.5) urine. Urine alkalinity was achieved and maintained by oral administration of up to 400 mg of sodium bicarbonate/kg/d, and acidity was achieved and maintained by oral administration of up to 400 mg of ammonium chloride/kg/d. Ampicillin sodium was measured in the plasma of horses by use of an agar diffusion microbiological assay with Bacillus subtilis as the test organism. T...
Post-transfusion survival of 50Cr-labeled erythrocytes in neonatal foals. Erythrocytes transfused allogeneically into mature horses have a short survival (less than 4 days) compared with an expected erythrocyte life span of 140-150 days. Yet, foals undergo transfusions for neonatal isoerythrolysis successfully. The authors have determined the survival of transfused erythrocytes in neonatal foals, using the stable isotope, 50Cr, to label the erythrocytes. Normal foals underwent transfusions with labeled erythrocytes from three sources: their own erythrocytes (autologous), the erythrocytes of their dam, and the erythrocytes of an unrelated castrated male. After transf...
Pharmacokinetics of phenobarbital in horses after single and repeated oral administration of the drug. Six healthy mature horses were orally administered a single dose of phenobarbital (26 mg/kg of body weight), then multiple doses (13 mg/kg) orally for 42 consecutive days. Seventeen venous blood samples were collected from each horse after the single dose study and again after the last dose on day 42. Plasma phenobarbital concentration was determined by use of a fluorescence assay validated for horses. Additional blood samples (n = 11) were collected on days 8 and 25 to determine peak and trough concentrations, as well as total body clearance. Phenobarbital disposition followed a one-compartme...
Clinical pharmacokinetics in veterinary medicine. Veterinary and human pharmacology differ principally in the range of species in which drugs are used and studied. In animals, as in humans, an understanding of the dose-effect relationship can be obtained by linking pharmacokinetic behaviour with pharmacodynamic information. Studies of different classes of drugs support the assumption that the range of therapeutic plasma concentrations in animals is generally the same as in humans. The requirement for species differences in dosage or administration rate (dose/dosage interval) may be attributed to variations in pharmacokinetic behaviour or phar...
Effect of probenecid on the pharmacokinetics of flunixin meglumine and phenylbutazone in healthy mares. Pharmacokinetic values for flunixin meglumine (1 mg/kg of body weight) and phenylbutazone (4 mg/kg) dosages were determined after a single IV injection with and without concurrent intragastric administration of probenecid (50 mg/kg) in 6 healthy mares. Significant difference was not apparent in the pharmacokinetic values of flunixin meglumine with and without concurrent probenecid administration. Significant (P less than or equal to 0.05) increase was evident in the 12-hour mean concentration of phenylbutazone (11.45 +/- 1.66 micrograms/ml without probenecid; 14.56 +/- 1.20 micrograms/ml with ...
Plasma elimination and urinary excretion of procaine after administration of different products to standardbred mares. Plasma and urinary concentrations of procaine were examined in Standardbred mares after subcutaneous administration of various doses (80 mg to 1600 mg) of procaine hydrochloride. Regardless of dose, peak plasma procaine values occurred within 1 h, but remained detectable in a dose-dependent manner, with procaine present at 1 h with the 80 mg dose and 6 h at the 1600 mg dose. Similarly, peak urinary procaine concentrations were attained within 1.5 to 3 h, irrespective of dose, while detection time was dose-dependent, being 23 h for 80-200 mg doses but as long as 30-54 h with the 1600 mg dose. W...
Influence of feeding schedule on the absorption of orally administered flunixin in the horse. The effects of access to hay and of restricted feeding on the pharmacokinetics of flunixin administered orally to six healthy ponies were compared in a cross-over study. No access to feed for a few hours before and after flunixin administration resulted in rapid absorption with a mean peak plasma concentration of 2.84 +/- 0.28 micrograms/ml attained in an average time of 0.76 +/- 0.18 h, followed by an exponential decline in plasma concentration. A lower peak plasma concentration was obtained when ponies had free access to hay before and after drug dosing. The mean maximum concentration (Cmax)...
The pharmacology and pharmacokinetics of high-dose methocarbamol in horses. The haemodynamic, respiratory and behavioural effects and pharmacokinetics of methocarbamol were studied in eight healthy, adult horses after intravenous (i.v.) and oral administration of large dosages. Heart rate, cardiac output, mean pulmonary arterial blood pressure, systolic, diastolic and mean aortic blood pressure, respiratory rate and arterial blood gases did not change after either i.v. (30 mg/kg bodyweight [bwt]) or oral (50 and 100 mg/kg bwt) dosages of methocarbamol. Mild to moderate depression was observed in five of eight horses administered i.v. methocarbamol, and in all horses a...
The influence of surgery and anaesthesia on the pharmacokinetics of pethidine in the horse. The plasma concentration of pethidine was measured in 16 horses, after its administration intravenously (i.v.) at a dose rate of 1 mg/kg bodyweight (bwt). In eight animals studied before surgery, the plasma levels of the drug decreased in a bi-exponential manner with a distributive half life of 3 mins and an elimination half life of 57.7 mins. Total body clearance was 17.7 ml/kg bwt/min. The remaining horses were investigated immediately after a period of anaesthesia and surgery and in these animals the drug exhibited smaller volumes of distribution (V1 cand Vdarea) and a significantly lower c...
Pharmacokinetics of tolfenamic acid in the horse. The pharmacokinetics of tolfenamic acid were studied in five ponies after an intravenous (iv) administration (2 mg/kg bodyweight [bwt]) and in four horses after an oral administration (30 mg/kg bwt) of tolfenamic acid. The plasma levels were determined by high pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). For the iv administration, a three-compartment model was used to represent the plasma concentration-time curve of the drug. The elimination half-life of the compound was 6.1 +/- 1.5 h, the total body clearance was 72.4 +/- 16.7 ml/kg bwt/h and the ste...
Pharmacokinetics and metabolism of intravenous doxapram in horses. The pharmacokinetics and metabolism of doxapram in horses administered intravenous (iv) doses of 0.275, 0.55 and 1.1 mg doxapram/kg bodyweight (bwt) were investigated. Plasma doxapram concentrations decreased rapidly after drug administration and the disappearance of doxapram from plasma was best described by a polyexponential equation. Median values of total body clearance were 10.9, 10.6 and 10.9 ml/min/kg bwt for the three doses and were independent of dose. The steady-state volume of distribution was approximately 1,200 ml/kg bwt and the median biological half-life ranged from 121 to 178 m...
Interference of maternal antibodies with the immune response of foals after vaccination against equine influenza. The purpose of the study was twofold. First, using two groups of 22 foals each, we investigated the extent to which maternal antibodies interfere with the humoral response against equine influenza. The foals were born to mares that had been vaccinated twice yearly against influenza since 1982. Foals of group I were vaccinated three times at early ages (12, 16, and 32 weeks of age), and foals of group II were likewise vaccinated but a later ages (24, 28, and 44 weeks of age). After the first and second vaccinations, neither group showed an increase in antibodies that inhibit haemagglutination. ...
The pharmacokinetics of a slow-release theophylline preparation in horses after intravenous and oral administration. The pharmacokinetics of a slow-release theophylline formulation was investigated following intravenous and oral administration at 10 mg/kg in horses. A tricompartmental model was selected to describe the intravenous plasma profile. The elimination half-life (t1/2 beta) was 16.91 +/- 0.93 h, the apparent volume of distribution (Vd) was 1.35 +/- 0.18 L/kg and the body clearance (ClB) was 0.061 +/- 0.009 L kg-1 h. After oral administration the half-life of absorption was 1.24 +/- 0.30 h, and the calculated bioavailability was above 100%. The t1/2 beta after oral administration was 18.51 +/- 1.75 ...
An estimate of melanosome concentration in pigment tissues. Concentration of melanosomes in various tissues has been unknown because of the impracticability of their direct quantification. Using an indirect approach comprising the estimation of melanin both in freeze-dried tissue samples and in isolated melanosomes, we obtained data on the amount of melanosomes in various pigment tissues. The concentrations of melanosomes found in the tissues were relatively high, not only reflecting the dark color of pigment tissues but also explaining their capacity to perform various functions ascribed to the presence of melanin.
Glyoxalase 2 deficiency in the erythrocytes of a horse: 1H NMR studies of enzyme kinetics and transport of S-lactoylglutathione. In mammalian red blood cells the metabolism of methylglyoxal, and some alpha-ketoaldehydes, takes place via two, generally, highly active enzymes, glyoxalase 1 and 2. The 1H NMR spin-echo spectra of horse erythrocytes, and the various reactants in the glyoxalase system, were characterized as a prelude to obtaining series of spectra in time courses of methylglyoxal metabolism. We characterized the kinetics of the enzyme system in red cells from a normal horse and also from one which had very low activity of glyoxylase 2. The kinetics of the reaction scheme, with methylglyoxal as the starting su...
Pharmacokinetics of caffeine and its metabolites in horses after intravenous, intramuscular or oral administration. The pharmacokinetics of caffeine (CAF) and its metabolites, dimethylxanthines, were examined in horses administered 2.5 mg/kg of CAF intravenously (i.v.), intramusculary (i.m.), or orally (p.o.). The plasma samples were extracted by Extrelut and the concentrations of CAF and metabolites were determined by high performance liquid chromatography (HPLC) with a short column. The pharmacokinetics of CAF after bolus i.v. injection were described by the assumption of a two-compartment model, and those of CAF after i.m. or p.o. administration were done by the assumption of a one-compartment model. The...
Effects of carbohydrates on the pharmacokinetics and biological activity of equine chorionic gonadotropin in vivo. The sialylation of eCG was examined to determine its influence on the in vivo metabolism and biological activity of the molecule. Sialic acid was decrementally removed from eCG by incubation with agarose-linked neuraminidase for varying time periods. Pharmacokinetic parameters for the disappearance of 4,000 IU (267 micrograms) of three desialylated eCG preparations (20%, 53%, and 80% sialic acid removed) and control eCG were determined in sheep. The clearance rate of eCG increased (p less than 0.05) with each decrement of sialic acid. The removal of 53% sialic acid enhanced the distribution of...
Clenbuterol plasma concentrations after repeated oral administration and its effects on cardio-respiratory and blood lactate responses to exercise in healthy Standardbred horses. To evaluate the effects of clenbuterol on cardio-respiratory parameters and blood lactate relation to exercise tolerance, experimental horses performed standardized exercise tests on a high-speed treadmill before and after administration of the drug. Clenbuterol was administered in feed to six healthy Standardbreds at a dose rate of 0.8 micrograms/kg b.wt twice daily for 5.5 days. Each horse was tested twice, without and with a respiratory mask, during two consecutive days. One week elapsed between the baseline tests without drug and the tests with clenbuterol treatment (each horse served as i...