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.
Pharmacokinetics of ticarcillin and clavulanic acid given in combination to adult horses by intravenous and intramuscular routes. The pharmacokinetics of ticarcillin and clavulanic acid following administration by the intravenous (i.v.) and intramuscular (i.m.) routes were investigated in six normal adult horses. Following i.v. administration, the ticarcillin disposition data conformed to a two-compartment model with an elimination half-life of 1.0 h. The disposition of clavulanic acid was described by a one-compartment model with an elimination half-life of 0.40 h. Following i.m. administration, the half-lives of both drugs were prolonged (ticarcillin 1.8 h, clavulanic acid 1.2 h). The bioavailability of ticarcillin was...
Enterohepatic circulation of lorazepam and acetaminophen conjugates in ponies. Adult female ponies (130-225 kg) with chronically implanted external biliary fistulas (T-tubes) participated in three-way cross-over studies using either i.v. lorazepam (10 mg) or acetaminophen (2 g), two model drugs biotransformed mainly by hepatic conjugative reactions. The objectives were to determine the systemic pharmacokinetics, urinary and biliary excretion and degree of enterohepatic circulation (EHC) of these compounds. Trial conditions were: A: EHC intact, with blood and urine, but not bile, collected after i.v. drug administration; B: EHC interrupted, with blood, urine and bile coll...
Probenecid infusion in mares: effect on para-aminohippuric acid clearance. Para-aminohippuric acid (PAHA, 0.1 mg/min/kg of body weight) was infused IV into 2 mares, followed by concurrent IV infusion of PAHA and probenecid (0.075, 0.15, 0.25, or 0.35 mg of probenecid/min/kg). Probenecid infusion reduced the clearance of PAHA at serum probenecid concentrations greater than 55 micrograms/ml. At 12-hour intervals, probenecid (in 5 repeated doses - 50, 75, 100, or 200 mg/kg) was administered by gavage to 2 mares. Mean serum probenecid concentration was greater than 55 micrograms/ml for all dosages. At dosages less than 200 mg/kg, accumulation of probenecid in the serum w...
The use of urea as a marker of body water in the nursing foal. Urea, compared with deuterium oxide (D2O) as a reference, was used as a body marker to estimate body water volume in ten 2-month old nursing foals. Plasma urea clearance was regular over 10 h and the R2 of the disappearance curve was between 0.93 and 0.98. Mean urea space was about 4% lower than D2O space, but the standard deviation of the proportion of water in body weight was higher with urea (3.8%) than with D2O (1.6%). Calculated urea entry rate was 49 mg/h/kg LW0.75.
The effect of oral L-carnitine supplementation on the muscle and plasma concentrations in the Thoroughbred horse. 1. L-carnitine was administered orally to thoroughbred horses for 58 days. 2. Acceptability and effects on plasma, muscle and urine concentration were studied. 3. Ten-60 g/day (as 2-3 doses) was acceptable with no deleterious effects. 4. One x 10 g L-carnitine significantly raised the plasma-free carnitine concentration (7 hr post) from 21.2 to 31.8 mumol/l; 2 x 30 g increased the mean to 36.5 mumol/l. 5. Plasma acetylcarnitine increased from approximately 1 to 5.5 mumol/l (7 hr post) on 2 x 30 g/day. 6. Muscle total carnitine was unchanged over 58 days. 7. Urinary output accounted for 3.5-7.5...
Effects of halothane anesthesia on the clearance of gentamicin sulfate in horses. Inhalation anesthetics decrease the clearance of some drugs that are eliminated by renal excretion. The purpose of the study reported here was to investigate the effects of halothane anesthesia on the pharmacokinetics and urinary excretion of gentamicin sulfate, using the horse as a model. Using a crossover design, pharmacokinetic values after a single IV dose of gentamicin (4 mg/kg) were compared in halothane-anesthetized and unanesthetized horses. Compared with unanesthetized horses, the anesthetized horses had significant decreases in total body clearance (P less than 0.01) and apparent vol...
Plasma heparin values and hemostasis in equids after subcutaneous administration of low-dose calcium heparin. Different doses of heparin were given to equids SC to establish 0.05 to 0.20 U of heparin/ml of plasma. Plasma heparin values and antithrombin III activities were assayed, using chromogenic substrate methods. Activated partial thromboplastin and thrombin times were determined, using conventional coagulation assays. Tests were run every hour (or every 2 hours for antithrombin III) for 12 hours from 5 groups of 5 equids each after single injection of 40, 60, 80, 100, or 125 U of calcium heparin/kg of body weight and from 11 equids after injection of 150 U of calcium heparin/kg. The smaller dose ...
Identification of a flunixin metabolite in the horse by gas chromatography-mass spectrometry. The main metabolite of flunixin, a hydroxylated product, has been identified by gas chromatography-mass spectrometry and 1H NMR spectroscopy in equine urine and plasma. The method also permits the qualitative monitoring of the urinary elimination of the drug and its metabolite. The two products are detected up to 175 and 54 h, respectively, after a single intravenous administration at the dose of 1 mg/kg. Simultaneous detection of the two compounds increases the reliability of anti-doping control analysis.
A pharmacokinetic study of phenobarbital in mature horses after oral dosing. The pharmacokinetics of phenobarbital were determined in six mature horses after a single oral dose. Horses were administered a 5.5 mg/kg of body weight oral dose of phenobarbital tablets. Based on the combined evaluation of i.v. and oral results, phenobarbital displayed two-compartment pharmacokinetics in the horse with a terminal half-life of 19.0 +/- 4.4 (mean +/- SD) h. This half-life is considerably shorter than those reported for dogs and humans. The steady-state volume of distribution (Vdss/F) and the total body clearance (Clt/F) of phenobarbital were 0.753 +/- 0.115 l/kg and 27.9 +/- 9...
Pharmacokinetics of xylazine in ponies: influence of yohimbine. Twenty healthy ponies were given i.v. 1.1 mg/kg of xylazine from 2 manufacturers and the pharmacokinetic parameters calculated from the disposition curves. The disposition curves for the 2 commercial preparations were not different. Yohimbine, an antagonist of the pharmacologic effects produced by xylazine, did not alter the disposition of xylazine in the plasma. A single i.v. bolus of xylazine was completely described in 17 of 20 animals by the biexponential equation: Cp = 1.30e(-0.3955t) + 0.58e(-0.033t) where Cp represents the concentration of xylazine in the plasma at time t (min). The t1/...
Distribution of cephapirin into a tissue chamber implanted subcutaneously in horses. The pharmacokinetics of cephapirin sodium and its distribution into a tissue chamber implanted subcutaneously in the neck of mature horses are described. Cephapirin was administered as an intravenous bolus dose of 20 mg/kg. The serum concentration vs time curve was best described by a two-compartment open model. Cephapirin disappeared from serum rapidly (t1/2 beta = 18.8 min), and had only a modest volume of distribution (Vd(area) approximately equal to 346 mg/kg, Vd(ss) approximately equal to 204 ml/kg). Total clearance was also rapid (approximately equal to 13 ml/min.kg). Concentrations of t...
Pharmacokinetics of dantrolene sodium in horses. The pharmacokinetics of dantrolene sodium were investigated in horses following both intravenous (2 mg/kg) and intragastric (4 mg/kg) administration. Two ponies also received dantrolene sodium intravenously (2 mg/kg) in a pilot study to obtain preliminary kinetic data and to determine urinary and biliary excretion of the intact drug. Distribution and elimination of dantrolene was rapid, resulting in an elimination half-life of 129 +/- 8 (SEM) min and a whole body clearance of 4.16 +/- 0.52 ml/min/kg. Following intragastric administration, dantrolene rapidly acheived peak concentrations within ...
Pharmacokinetics of phenolsulfonphthalein in horse and pony mares. Pharmacokinetics of phenolsulfonphthalein (PSP) in horse and pony mares was determined after injection of 1 mg/kg of body weight, IV. A plasma PSP concentration vs time curve was described adequately in horses and ponies by an open, 2-compartment model. There were significant differences in the elimination phase parameters, apparent volume of distribution at steady state, and apparent volume of distribution of horses and ponies. The harmonic mean elimination half-life of PSP in horses was significantly longer (P less than 0.001) than that in the ponies (16.4 and 10.0 minutes, respectively). Th...
Measurement of flunixin in equine inflammatory exudate and plasma by high performance liquid chromatography. An accurate and reliable method for the separation of flunixin from, and measurement in, equine inflammatory exudate and plasma by high performance liquid chromatography has been developed. Flunixin can be detected in concentrations as low as 0.05 micrograms/ml using an ultraviolet spectrophotometric detector at 285 nm. Samples were acidified with 2M hydrochloric acid and extracted with dichloromethane. The extract was evaporated and reconstituted in acetonitrile. Iminodibenzyl was used as internal standard. The mean recovery of flunixin from plasma was 97.6 +/- 3.9 per cent. Particular advant...
Biological and immunological properties of zebra pituitary gonadotropins: comparison with horse and donkey gonadotropins. Previous studies from this laboratory have described the properties of purified luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from horse and donkey anterior pituitary glands. The present study afforded the opportunity to further characterize these previously purified hormone preparations and to compare them with enriched gonadotropin fractions from zebra pituitary glands. Although a single LH and FSH fraction was usually obtained for each pool of pituitaries, two separate zebra LH and two donkey FSH preparations were generated. Purified hormone preparations from the horse wer...
Pharmacokinetics and serum concentrations of cephapirin in neonatal foals. Six healthy foals, from 4 to 6 days of age, were given a single IM injection of sodium cephapirin (250 mg/ml) at a rate of 20 mg/kg of body weight. Serum concentrations of cephapirin were measured serially over an 8-hour period. The mean peak serum concentration was 21.2 micrograms/ml at 10 minutes. The overall elimination rate constant was 1.06/hr and the elimination half-life was 0.70 hour. The apparent volume of distribution at steady state was 1.06 L/kg and plasma clearance was 1,105 ml/hr/kg.
Pharmacokinetics of phenobarbital in the horse. Pharmacokinetics of phenobarbital was examined in 6 mature horses after 12 mg of phenobarbital/kg of body weight was infused over 20 minutes. Biexponential decrease in serum phenobarbital concentrations was observed with a distribution-phase half-life of 0.101 +/- 0.086 hour (mean +/- SD) and a terminal-phase elimination half-life of 18.3 +/- 3.65 hours. The volume of distribution at steady state was 0.803 +/- 0.070 L/kg. Total body clearance of phenobarbital was 30.8 +/- 6.2 ml/h/kg. The high clearance in the horse seems to explain the markedly shorter half-life of phenobarbital in this speci...
Absorption of neomycin from the equine uterus: effect of stage of oestrous cycle and volume of vehicle. Plasma concentrations of neomycin were measured following intrauterine infusion of 3.3 mg/kg bodyweight neomycin sulphate. Mares in oestrus absorbed approximately 6 per cent of neomycin infused whereas mares in a luteal phase absorbed 56 per cent. The volume of infusate also affected absorption as increased volume resulted in decreased absorption. The decreased absorption both during oestrus and when large volumes were used was probably due to reflux of antibiotic through the cervix.
Presence of salicylic acid in standardbred horse urine and plasma after various feed and drug administrations. Plasma and urinary levels of salicylic acid were examined in Standardbred mares after administration of various feeds, containing different compositions of hay. In addition, horses were administered acetylsalicylic acid orally and methyl salicylate topically. Elevated salicylic acid levels were observed in horse urine and plasma in animals fed lucerne hay. The plasma and urinary elimination of salicylic acid exhibited a diurnal pattern which was related to the type of feed and the feeding schedule. Within 24 h after oral administration of acetylsalicylic acid, plasma and urine salicylic acid l...
Low dose flunixin meglumine: effects on eicosanoid production and clinical signs induced by experimental endotoxaemia in horses. The efficacy of low doses of flunixin meglumine in reducing eicosanoid generation and clinical signs in response to experimentally induced endotoxaemia was investigated. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in serum and plasma by radioimmunoassay. Plasma flunixin concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters derived non-compartmentally. In horses administered flunixin meglumine before endotoxin challenge, a significant suppression in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha generation was observe...
Principles of drug disposition in the horse. This article is intended to give the reader an understanding of the mathematic and conceptual framework underlying equine pharmacology. The methods by which the veterinary practitioner determines drug concentrations, disposition, and bioavailability are discussed.
The bioavailability of phenylbutazone in the horse. [phenyl-14C]-Phenylbutazone was administered to 2 horses p.o. and i.v. on separate occasions. Plasma levels and urinary and faecal elimination of 14C were monitored for up to 7 days after dosing. Phenylbutazone was rapidly and extensively absorbed after oral administration, and its bioavailability was 91% assessed by comparison of plasma AUCs of unchanged drug after p.o. and i.v. administration. The plasma elimination half-life of phenylbutazone was 9.7 h and this was independent of the route of administration. The pattern of elimination of phenylbutazone was independent of the route of admini...
Pharmacokinetics of intravenously administered ketamine in the horse. The metabolism and distribution of ketamine and its two major metabolites (norketamine and dehydronorketamine) was investigated in 10 horses undergoing airway surgery. Following premedication with xylazine (1.1 mg kg-1 intravenously) anaesthesia was induced by the rapid injection of ketamine at a dose of 2.2 mg kg-1 intravenously. Anaesthesia was maintained with halothane vaporized in oxygen and nitrous oxide (50:50). Serially collected blood samples were analysed by a sensitive gas liquid chromatographic technique. Plasma ketamine concentrations declined biexponentially with a rapid initial d...
Pharmacokinetics of antipyrine, acetaminophen and lidocaine in fed and fasted horses. Previous studies demonstrated that plasma clearance of organic anions such as bilirubin, bile acid, sulfobromophthalein (BSP) and indocyanine green (ICG), was reduced from 36% (bile acid) to 55% (ICG) in fasted (3 days) horses. It is believed that a general decline in carrier-mediated hepatic uptake may have accounted for those changes. However, fasting may also affect hepatic blood flow, thereby contributing to reduced clearance of these compounds. In order to test this hypothesis, plasma clearance of antipyrine, acetaminophen and lidocaine, drugs known to be cleared by the liver yet not susp...