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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.
Equine lutropin and chorionic gonadotropin bear oligosaccharides terminating with SO4-4-GalNAc and Sia alpha 2,3Gal, respectively. Equine chorionic gonadotropin (eCG) and lutropin (eLH) are heterodimeric glycoprotein hormones which are synthesized in the placenta and pituitary, respectively. The beta subunits of eCG and eLH, like their alpha subunits, arise from a single gene and have identical amino acid sequences. In contrast, the beta subunits of CG and LH in primates arise from different genes and differ in sequence. We have examined the structures of the Asn-linked oligosaccharides on eCG and eLH. eCG bears di- and tri-branched Asn-linked oligosaccharides terminating with Sia alpha 2,3 or 6Gal beta 1,4GlcNAc. In cont...
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...
Structural changes in intercellular junctions during keratinization of the stratum medium of the equine hoof wall. Cells of the intertubular horn of the stratum medium of the equine hoof wall are joined by three types of junctions. Desmosomes and gap junctions were present in all strata. Septate-like junctions and an intercellular line were seen in the distal stratum spinosum subsequent to extrusion of the contents of membrane-coating granules. At a later stage of keratinization, non-membrane-bound acid phosphatase reaction product appeared to leak into the intercellular space except into areas occupied by septate-like junctions and the intercellular line. It is proposed that the formation of septate-like ...
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...
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...
Effects of high-intensity exercise on plasma catecholamines in the thoroughbred horse. In Study 1, a single speed test of 6 to 12 m/sec was performed for 2 mins at an incline of 5 degrees on a high-speed treadmill (single-step test). Only one speed was performed per session and blood samples were taken before and after the test. In Study 2 horses cantered for 1 min at increasing speeds of 6 to 13 m/sec on an incline of 3 degrees (multiple-step test). Blood samples were taken before exercise, throughout the test and during recovery. In the single-step test plasma concentrations of adrenaline and noradrenaline both increased at speeds of 9 m/sec, as did blood lactate. Mean concent...
Ultrastructure of cilia in horses. This paper presents some ultrastructural details of cilia from the ciliated tracheal epithelium of healthy horses. By using a new fixation method, the Authors were able to describe minute details, some of which have been only rarely observed in other species and mostly by means of the freeze-etch technique (i.e. electron dense particles of ciliary necklace). The Authors justify the need to investigate the ultrastructural details of cilia in various species since the minute morphological differences might be functionally significant.
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...
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...
