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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.
Statistical evaluation of the regulatory guidelines for use of furosemide in race horses. The pharmacokinetic behavior of furosemide concentrations in performance horses is of great interest to the equine industry and equine researchers. Specifically, such information is useful for the evaluation of the existing guidelines in several racing jurisdictions and for the possible development of new guidelines for varying time periods after administration. We studied several approaches within the framework of nonlinear mixed effects models to increase the accuracy of evaluating these guidelines. Theoretical properties of the proposed methods were examined and the variances of the resulti...
Pharmacokinetics of gentamicin in mares in late pregnancy and early lactation. The disposition of drugs may differ between pregnant and nonpregnant animals, necessitating a change in dosage. We hypothesized that volume of distribution or clearance may be different for aminoglycoside antibiotics in pregnant mares vs. nonpregnant lactating mares. To examine this hypothesis, we administered gentamicin sulfate to seven Thoroughbred and Quarterhorse mares on two occasions, followed by plasma drug gentamicin assay and pharmacokinetic analysis. The first dose was administered 1-4 weeks before parturition (mean weight 578 kg) and the second dose was administered in the period 1-...
Administration of ticarcillin in combination with clavulanic acid intravenously and intrauterinely to clinically normal oestrous mares. Ticarcillin and clavulanic acid (potassium clavulanate) were administered to normal oestrous mares intravenously (i.v.) at a dose of 50 and 1.67 mg/kg for ticarcillin and clavulanate, respectively. In a crossover design, the same drugs were administered intrauterine (i.u.) at a dose of 12.4 and 0.4 mg/kg for ticarcillin and clavulanate, respectively. The i.u. dose was administered in 100 mL of saline solution. Endometrial tissue biopsies and plasma samples were collected after drug administration for the determination of ticarcillin and clavulanate concentrations by high-pressure liquid chroma...
Pharmacokinetics of metronidazole in horses after intravenous, rectal and oral administration. Metronidazole pharmacokinetics in horses was studied after intravenous (i.v.), rectal (p.r.) and oral (p.o.) administration at 20 mg/kg using a triple crossover study design. Metronidazole mean+/-SD half-life was 196+/-39, 212+/-30 and 240+/-65 min after i.v., p.r. and p.o. administration, respectively. The metronidazole clearance was 2.8 (mL/min/kg) and the volume of distribution at steady state was 0.68 L/kg. The pharmacokinetic parameters calculated for metronidazole after administration of the drug by the various routes showed that bioavailability (74+/-18 vs. 30+/-9%) and maximum serum co...
Comparative disposition of tripelennamine in horses and camels after intravenous administration. The pharmacokinetics of tripelennamine (T) was compared in horses (n = 6) and camels (n = 5) following intravenous (i.v.) administration of a dose of 0.5 mg/kg body weight. Furthermore, the metabolism and urinary detection time was studied in camels. The data obtained (median and range in brackets) in camels and horses, respectively, were as follows: the terminal elimination half-lives were 2.39 (1.91-6.54) and 2.08 (1.31-5.65) h, total body clearances were 0.97 (0.82-1.42) and 0.84 (0.64-1.17)L/h/kg. The volumes of distribution at steady state were 2.87 (1.59-6.67) and 1.69 (1.18-3.50) L/kg, ...
Pharmacokinetics and metabolic effects of triamcinolone acetonide and their possible relationships to glucocorticoid-induced laminitis in horses. Experiments were performed to establish the pharmacokinetics of triamcinolone acetonide and the effects of the glucocorticoid on glucose metabolism in horses. The pharmacokinetics after intravenous (i.v.) dosing was best described by a three-compartment open model. There was rapid distribution from the central compartment followed by two phases of elimination. The half-life of the rapid elimination phase was 83.5 min and of the slower phase was 12 h. The term (Vss/Vc)-1was 12.3 indicating extensive distribution into the tissues. Triamcinolone acetonide given i.v. or intramuscularly (i.m. ) ind...
Pharmacokinetics of propranolol and its metabolites in horses after intravenous or oral administration. The pharmacokinetics characteristics of propranolol (PPL) in horses was studied by administering the drug intravenously or orally to the animals. The predominant primary pathway was ring oxidation, and 4-hydroxypropranolol glucuronide (4-OHPG) was the major metabolite in both plasma and urine. Side-chain glucuronidation and oxidation were not significant. A two-compartment model was employed for PPL followed by a one-compartment model for 4-OHPG. After oral administration, one-step absorption and two-step first pass metabolism were employed. The fraction absorbed of PPL was approximately 70% a...
Pharmacokinetics of acetazolimide after intravenous and oral administration in horses. To determine the pharmacokinetics of acetazolamide administered IV and orally to horses. Methods: 6 clinically normal adult horses. Methods: Horses received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and blood samples were collected at regular intervals before and after administration. Samples were assayed for acetazolamide concentration by high-performance liquid chromatography, and concentration-time data were analyzed. Results: After IV administration of acetazolamide, data analysis revealed a median mean residence time of 1.71 +/- 0.90 hours and median total body c...
Pharmacokinetics of penicillin G procaine versus penicillin G potassium and procaine hydrochloride in horses. To compare the pharmacokinetics of penicillin G and procaine in racehorses following i.m. administration of penicillin G procaine (PGP) with pharmacokinetics following i.m. administration of penicillin G potassium and procaine hydrochloride (PH). Methods: 6 healthy adult mares. Methods: Horses were treated with PGP (22,000 units of penicillin G/kg of body weight, i.m.) and with penicillin G potassium (22,000 U/kg, i.m.) and PH (1.55 mg/kg, i.m.). A minimum of 3 weeks was allowed to elapse between drug treatments. Plasma and urine penicillin G and procaine concentrations were measured by use of...
Cerebrospinal fluid and blood concentrations of toltrazuril 5% suspension in the horse after oral dosing. Toltrazuril 5% suspension (Baycox, Bayer Canada, Ontario, Canada) was administered to six adult horses followed by blood collection and assay to determine the concentration of toltrazuril and its principal metabolites, toltrazuril sulfone and toltrazuril sulfoxide. From this data, the maximum concentration (C(max)), elimination half-life (T 1/2), and mean residence times of the plasma were determined from standard pharmacokinetic formulas. After a single oral dose of 10 mg/kg body weight a rapid absorption was found, with a mean peak serum concentration of 11.17 mg/L at 18 hours. Elimination w...
Melanin affinity: a possible explanation of isoxsuprine retention in the horse. Isoxsuprine is used in veterinary medicine as a vasodilating agent. The drug has been detected in the urine of horses up to 6 weeks after the cessation of administration. In the present study, the distribution pattern of 3H-isoxsuprine was investigated using whole body autoradiography in mice to find a possible site of retention. Melanin was the only place of retention identified. Additional in vitro studies showed an affinity of isoxsuprine to both melanin and keratin. The K(d) values were 0.02 mmol/l and 1 mmol/l, and the B(max) values were 0.2 micromol/mg and 2 micromol/mg, respectively. A ...
Effects of intramuscular omeprazole on gastric acid secretion in horses over a twenty-four hour period. The effect of intramuscular (i.m.) omeprazole (0.25 or 1.0 mg/kg bwt; LD and HD), respectively, on volume, total acid output (TAO) and pH of the gastric juice was studied during 24 h in 5 horses with a chronically implanted gastric cannula. Whether secretion in controls was basal or stimulated with pentagastrin (8 micrograms/kg bwt/h), volume (NS) and TAO (P < 0.01, NS) gradually decreased and pH increased (P < 0.05, NS). Omeprazole significantly reduced the average basal TAO by 49 +/- 6% (LD) and 88 +/- 3% (HD) and the stimulated TAO by 64 +/- 2% and 97 +/- 1%. Basal pH in controls was ...
Use of 99mTc-mercaptoacetyltriglycine to evaluate renal function in horses. Ten healthy horses were injected intravenously with 99mTc-MAG3 and the disappearance of radioactivity from the blood was measured. The total body clearance (Cl(B)) and elimination half-life (t1/2(beta)) were 7.9 +/- 1.5 ml/kg/minute and 32.8 +/- 4.1 minutes, respectively. The disappearance of 99mTc-MAG3 from the blood of 2 horses with compromised renal function was also measured. The data suggest that 99mTc-MAG3 is a useful and clinically applicable radiopharmaceutical for measurement of effective renal blood flow in the horse.
Diclazuril in the horse: its identification and detection and preliminary pharmacokinetics. Diclazuril (4-chlorophenyl [2,6-dichloro-4-(4,5-dihydro-3H-3,5-dioxo-1,2,4-triazin-2-yl)pheny l] acetonitrile), is a benzeneacetonitrile antiprotozoal agent (Janssen Research Compound R 64433) marketed as Clinacox . Diclazuril may have clinical application in the treatment of Equine Protozoal Myeloencephalitis (EPM). To evaluate its bioavailability and preliminary pharmacokinetics in the horse we developed a sensitive quantitative high-pressure liquid chromatography (HPLC) method for diclazuril in equine biological fluids. MS/MS analysis of diclazuril in our HPLC solvent yielded mass spectral ...
Pharmacokinetics of flunixin meglumine in donkeys, mules, and horses. To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. Methods: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. Methods: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumi...
Pharmacokinetic interactions between flunixin and sulphadimidine in horses. The pharmacokinetic aspects of sulphadimidine were studied in clinically healthy (control) and Flunixin-medicated horses after a single intravenous and oral administration of 100 mg/kg body weight. Plasma sulphadimidine concentration were determined by high-performance liquid chromatography (HPLC). Following the intravenous injection, all plasma sulphadimidine data were best approximated by a two-compartment open model using sequential, weight non-linear regression. Flunixin induced a 67% increase in the rate of sulphadimidine return to the central compartment from peripheral tissues (K21) and...
PGFM response to exogenous oxytocin and determination of the half-life of oxytocin in nonpregnant mares. We investigated the half-life of oxytocin in reproductively normal mares and the prostaglandin response after oxytocin administrations. Mares were given oxytocin, 10 or 25 iu, i.v., on the day of, or 2 days after, ovulation, and frequent jugular blood samples were collected for analysis of oxytocin and Prostaglandin F metabolite (PGFM) by RIA. Neither dose of oxytocin nor day of treatment affected the half-life of the exogenous oxytocin, which was determined to be 6.8 min. A significant increase in PGFM was observed within 6 min of oxytocin administration and peak values were observed within 1...
Pharmacokinetics of carprofen enantiomers in equine plasma and synovial fluid – a comparison with ketoprofen. Carprofen is a Non Steroidal Anti-Inflammatory Drug (NSAID) which is widely used for the treatment of musculoskeletal disorders in horses. The commercial preparation is a racemic mixture of two enantiomers (R and S carprofen). We used HPLC to measure plasma and synovial fluid R and S carprofen concentrations following a single intravenous (i.v.) dose, and computer modelling to determine the pharmacokinetic parameters of the enantiomers in these two body fluids. A comparison was made with results from an identical experiment using ketoprofen. The plasma elimination half lives of R and S carprof...
The elimination profiles of tenoxicam and hydroxytenoxicam in equine urine and serum after a 200-mg oral dose. Tenoxicam (Mobiflex) was administered orally to four standardbred mares at a dose of 200 mg. Elimination profiles of tenoxicam and hydroxytenoxicam were generated based on quantitation of these analytes in urine and serum by liquid chromatography (LC) with ultraviolet detection. Tenoxicam was confirmed by LC-tandem mass spectrometry daughter ion mass spectra in the last postadministration sample in which tenoxicam was detected. The tenoxicam and hydroxytenoxicam urinary elimination profiles had the same shape for the same horse; however, each horse was significantly different from the others. ...
Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation. The pharmacokinetics of intravenous (i.v.) medetomidine (7 mcg kg(-1)) were best described by a two-compartment model in five ponies. Total body clearance was 4 (SD 0.60) 1 kg h,(-1)t(1/2alpha)7. 6 (0.91) minutes and t(1/2beta)51.3 (13.09) minutes. In one pony the one-compartmental model was best fit, and total body clearance was 4. 2 l kg h(-1)and t(1/2)was 11 minutes. Medetomidine plasma levels had fallen below the limits of quantification (0.05 ng ml(-1)) within 4 hours. Medetomidine 5 mcg kg(-1)i.v. followed by an infusion of 3.5 mcg kg h(-1)for two hours provided a constant level of sedat...
A pharmacodynamic and pharmacokinetic study with vedaprofen in an equine model of acute nonimmune inflammation. The pharmacodynamics and enantioselective pharmacokinetics of vedaprofen were studied in six ponies in a two period cross-over study, in which a mild acute inflammatory reaction was induced by carrageenan soaked sponges implanted subcutaneously in the neck. Vedaprofen, administered intravenously at a dosage of 1 mg/kg, produced significant and prolonged inhibition of ex vivo serum thromboxane B2 (TXB2) synthesis and short-lived inhibition of exudate prostaglandin E2 (PGE2) and TXB2 synthesis. Vedaprofen also partially inhibited oedematous swelling and leucocyte infiltration into exudate. Vedap...
Transferability of cephalothin to the alveolar cavity in thoroughbreds. Five Thoroughbreds were classified into 4 groups according to the administration method used for saline solution (saline), ambroxol, and cephalothin sodium (cephalothin). In group A, cephalothin was injected intravenously after oral administration of ambroxol. In group B, cephalothin was injected intravenously after oral administration of saline. Groups C and D were used as control groups. The dose of cephalothin or ambroxol was clinically administrated. Venous blood and bronchoalveolar lavage fluid (BALF) were sampled from each group. In groups A and B, cephalothin concentrations in plasma re...
Extraction of equine chorionic gonadotrophin from pregnant mare plasma by direct adsorption on chromatographic media. Equine chorionic gonadotrophin (eCG) is a hormone of practical value in veterinary medicine and animal production. Here we report a novel preparation procedure based on its direct adsorption onto anionic-exchange resins in a batch-wise mode. The active plasma is previously conditioned to reduce pH and ionic strength to required levels. After the adsorption stage, a 90% recovery of the initial eCG is achieved, with a concentration factor of about 50 and an enrichment factor around 500, with high preservation of biological activity. Further purification is carried out by cation-exchange column c...
The urinary elimination profiles of diazepam and its metabolites, nordiazepam, temazepam, and oxazepam, in the equine after a 10-mg intramuscular dose. A method for the extraction of diazepam and its metabolites (nordiazepam, temazepam, and oxazepam) from equine urine and serum and their quantitation and confirmation by liquid chromatography-tandem mass spectrometry is presented. Valium, a formulation of diazepam, was administered at a dose of 10 mg intramuscularly to four standard-bred mares. Diazepam is extensively metabolized in the horse to nordiazepam, temazepam, and oxazepam. Diazepam urinary concentrations were found to be less than 6 ng/mL. Nordiazepam was found to be mainly in its glucuronide-conjugated form and was measured out to a...
Exploring the possible functions of equine hoof wall tubules. Possible functions of equine hoof wall tubules were investigated in this study. Hydration tests were conducted on blocks of hoof wall tissue in order to test the hypothesis that hollow tubules facilitate the conduction of water vapour distally. Although water loss or gain was inhibited through the outer wall surface, the increase in surface area provided by medullary spaces was ineffective in facilitating hydration through the face with exposed tubule ends. Rather, hollow tubules appear to allow for a higher dehydration rate through their exposed ends. Analysis of medullary space indicates tha...
