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 and metabolism of orally administered firocoxib, a novel second generation coxib, in horses. The primary objective of this study was to determine the pharmacokinetic profile of firocoxib, a novel second generation coxib, in horses. Horses were administered either a single oral or intravenous dose of firocoxib at 0.1 mg/kg in a two-period crossover study with 12 animals. The dosage was based on previously determined pharmacodynamic parameters. Oral firocoxib was well absorbed with an average bioavailability (absolute) of 79% and a Cmax of 75 ng/mL at 3.9 h. The average elimination half-life was 30 h. Following intravenous administration the average Cmax was 210 ng/mL and the eliminatio...
Cetirizine in horses: pharmacokinetics and effect of ivermectin pretreatment. The pharmacokinetics of the histamine H(1)-antagonist cetirizine and the effects of pretreatment with the antiparasitic macrocyclic lactone ivermectin on the pharmacokinetics of cetirizine were studied in horses. After oral administration of cetirizine at 0.2 mg/kg bw, the mean terminal half-life was 3.4 h (range 2.9-3.7 h) and the maximal plasma concentration 132 ng/mL (101-196 ng/mL). The time to reach maximal plasma concentration was 0.7 h (0.5-0.8 h). Ivermectin (0.2 mg/kg bw) given orally 1.5 h before cetirizine did not affect its pharmacokinetics. However, ivermectin pretreatment 12 h be...
Pharmacokinetics and in vitro effects of tegaserod, a serotonin 5-hydroxytryptamine 4 (5-HT4) receptor agonist with prokinetic activity in horses. Tegaserod, a serotonin agonist, has been shown to have prokinetic effects in horses, but pharmacokinetic information is not currently available. The pharmacokinetics and in vitro effects of tegaserod were evaluated. Tegaserod increased the contractile activity of smooth muscle preparations of the equine pelvic flexure. Pertinent pharmacokinetic parameters for a single IV and oral dose were determined. Therapeutic plasma concentrations of tegaserod were achieved by a single oral dose at 0.27 mg/kg. These findings indicate that further clinical studies are warranted to investigate potential bene...
Influence of training on plasma adrenaline and noradrenaline kinetics in untrained standardbreds. Catecholamines (CAT) play an important role in modulating the response to exercise. But the kinetics of CAT changes during exercise are difficult to study due to their short biological half-life. Objective: Learning about variations in plasma CAT levels during training could furnish new information regarding sweating, redistribution of blood flow and energy metabolism. Methods: Four untrained Standardbreds, adapted to treadmill work, were used to determine the influence of training on plasma adrenaline (A) and noradrenaline (NA) kinetics. Horses underwent a standardised exercise test (SET) on ...
Pharmacokinetics of boldenone and stanozolol and the results of quantification of anabolic and androgenic steroids in race horses and nonrace horses. Anabolic steroids (ABS) boldenone (BL; 1.1 mg/kg) and stanozolol (ST; 0.55 mg/kg) were administered i.m. to horses and the plasma samples collected up to 64 days. Anabolic steroids and androgenic steroids (ANS) in plasma were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The limit of detection of all analytes was 25 pg/mL. The median absorption (t1/2 partial differential) and elimination (t1/2e) half-lives for BL were 8.5 h and 123.0 h, respectively, and the area under the plasma concentration-time curve (AUCho) was 274.8 ng.h/mL. The median t1/2e for ST was 82.1 ...
Pulmonary disposition of erythromycin, azithromycin, and clarithromycin in foals. The objectives of the present study were to determine and compare the pulmonary disposition of azithromycin, clarithromycin, and erythromycin in foals. A single dose (10 mg/kg) of azithromycin, clarithromycin, or erythromycin was administered intragastrically to six healthy 1- to 3-month-old foals using an orthogonal design. Activity of the drugs was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells by use of a microbiologic assay. Peak drug activity in PELF was significantly higher in foals treated with clarithromycin (48.96+/-13.26 microg/mL)...
Pharmacokinetics of etodolac in the horse following oral and intravenous administration. The purpose of this study was to determine the pharmacokinetics of etodolac following oral and intravenous administration to six horses. Additionally, in vitro cyclooxygenase (COX) selectivity assays were performed using equine whole blood. Using a randomized two-way crossover design, horses were administered etodolac (20 mg/kg) orally or intravenously, with a minimum 3-week washout period. Plasma samples were collected after administration for analysis using high pressure liquid chromatography with ultraviolet detection. Following intravenous administration, etodolac had a mean plasma half-li...
Pharmacokinetics of altrenogest in horses. The Federation Equestre Internationale has permitted the use of altrenogest in mares for the control of oestrus. However, altrenogest is also suspicious to misuse in competition horses for its potential anabolic effects and suppression of typical male behaviour, and thus is a controlled drug. To investigate the pharmacokinetics of altrenogest in horses we conducted an elimination study. Five oral doses of 44 mug/kg altrenogest were administered to 10 horses at a dose interval of 24 h. Following administration blood and urine samples were collected at appropriate intervals. Altrenogest concentr...
Pharmacokinetics of fentanyl delivered transdermally in healthy adult horses–variability among horses and its clinical implications. The safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60-67 microg/kg, were investigated in six healthy adult horses. Three transdermal fentanyl patches (Duragesic), each containing 10 mg of fentanyl citrate, were applied to the mid-dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it...
Persistence of serum antibodies to Sarcocystis neurona in horses moved from North America to India. The study reported here was undertaken to assess the presence of antibodies to Sarcocystis neurona in the serum of horses of North American origin that had been relocated for 1 year or more to India (ie, outside of the known endemic areas for S. neurona). Objective: The presence or absence of such antibodies should provide information concerning the persistence of such antibodies, or support the presence of chronic infection, or both. Methods: A total of 228 Thoroughbred horses were sampled in India, of which 86 were of North American origin that had been in India between 1 and 13 years, 124 w...
The adrenocorticotropin stimulation test: contribution of a physiologically based model developed in horse for its interpretation in different pathophysiological situations encountered in man. The present study aimed to characterize the adrenal response to ACTH. A model was developed that coupled the nonlinear disposition of cortisol with a physiologically based model for cortisol secretion by the adrenals. It was assumed that the response to ACTH resulted from two mechanisms: a stimulation of the cortisol secretion rate and control of the duration of the secretion. Seven dose levels of ACTH were tested in horses, a species similar to man as regards adrenal function. The main result was that the secretion rate of the adrenal gland can be modelized by a zero order process that is max...
Pharmacokinetics of voriconazole after oral and intravenous administration to horses. To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution. Methods: 6 adult horses. Methods: Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed. Results: Voriconazole was adequately absorbed after oral administration in horses, with a s...
Pharmacokinetics of the calcium-channel blocker diltiazem after a single intravenous dose in horses. The pharmacokinetics of diltiazem were determined in eight healthy horses. Diltiazem HCl, 1 mg/kg i.v., was administered over 5 min. Venous blood samples were collected at regular intervals after administration. Plasma concentrations of diltiazem and desacetyldiltiazem were determined by high-performance liquid chromatography. A second, putative metabolite was detected, but could not be identified due to the lack of an authentic standard. Data were analyzed by nonlinear least-squares regression analysis. The median (minimum-maximum) peak plasma concentration of diltiazem was 727 (539-976) ng/m...
Pharmacokinetics of methylprednisolone acetate after intra-articular administration and its effect on endogenous hydrocortisone and cortisone secretion in horses. To determine the pharmacokinetics of methylprednisolone (MP) and develop a pharmacokinetic-pharmacodynamic model of the related changes in plasma concentrations of endogenous hydrocortisone (HYD) and cortisone (COR) following intra-articular administration of methylprednisolone acetate (MPA) in horses. Methods: 6 Thoroughbreds. Methods: In each horse, 200 mg of MPA was injected intrasynovially into a carpal joint, and plasma MP, HYD, and COR concentrations were determined via liquid chromatography-mass spectrometry. Results: A 5-compartment pharmacokinetic-pharmacodynamic model was used to des...
Evaluation of the pharmacokinetics and bioavailability of intravenously and orally administered amiodarone in horses. To determine the clinical effects and pharmacokinetics of amiodarone after single doses of 5 mg/kg administered orally or intravenously. Methods: 6 healthy adult horses. Methods: In a cross over study, clinical signs and electrocardiographic variables were monitored and plasma and urine samples were collected. A liquid chromatography-mass spectrometry method was used to determine the percentage of protein binding and to measure plasma and urine concentrations of amiodarone and the active metabolite desethylamiodarone. Results: No adverse clinical signs were observed. After IV administration, m...
Pharmacokinetics and tissue distribution of itraconazole after oral and intravenous administration to horses. To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution. Methods: 6 healthy horses. Methods: Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconaz...
Pharmacokinetics of azathioprine following single-dose intravenous and oral administration and effects of azathioprine following chronic oral administration in horses. To determine pharmacokinetics of azathioprine (AZA) and clinical, hematologic, and serologic effects of i.v. and oral administration of AZA in horses. Methods: 6 horses. Methods: In study phase 1, a single dose of AZA was administered i.v. (1.5 mg/kg) or orally (3.0 mg/kg) to 6 horses, with at least 1 week between treatments. Blood samples were collected for AZA and 6-mercaptopurine (6-MP) analysis 1 hour before and at predetermined time points up to 4 hours after AZA administration. In study phase 2, AZA was administered orally (3 mg/kg) every 24 hours for 30 days and then every 48 hours for ...
A pilot study on the transfer of 137Cs and 90Sr to horse milk and meat. The radiological assessment of the impact of nuclear weapon's testing on the Semipalatinsk Test Site (STS) on the local population requires comprehensive site-specific information on radionuclide behaviour in the environment. However, information on radionuclide behaviour in the conditions of the STS is rather sparse and, in particular, there are no data in the literature on parameters of radionuclide transfer from feed to horse products proofed to be important contributors to the internal dose to the local population. The transfer of 137Cs and 90Sr to horse milk and meat was studied under lab...
Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration. The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high-pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half-life (t(1/2)) of 2.02 h and volume o...
Deprotonation of the horse liver alcohol dehydrogenase-NAD+ complex controls formation of the ternary complexes. Binding of NAD+ to wild-type horse liver alcohol dehydrogenase is strongly pH-dependent and is limited by a unimolecular step, which may be related to a conformational change of the enzyme-NAD+ complex. Deprotonation during binding of NAD+ and inhibitors that trap the enzyme-NAD+ complex was examined by transient kinetics with pH indicators, and formation of complexes was monitored by absorbance and protein fluorescence. Reactions with pyrazole and trifluoroethanol had biphasic proton release, whereas reaction with caprate showed proton release followed by proton uptake. Proton release (200-55...
Pharmacokinetics of imipenem-cilastatin following intravenous administration in healthy adult horses. In two studies, six healthy adult horses were given imipenem-cilastatin by slow intravenous (i.v.) infusion at an imipenem dosage of 10 mg/kg (study 1) and 20 mg/kg (study 2). The same horses were used in each dosage schedule, with a 2-week washout period between studies. In each dosage group, serial blood and synovial fluid samples were collected for 6 h after completion of the infusion. HPLC was used to determine the imipenem concentration in all samples. Imipenem was well tolerated by all horses at both dosages; no adverse effects were noted during the study period or during the 24-hour pos...
Heterogeneous clearance of antithymocyte globulin after CD34+-selected allogeneic hematopoietic progenitor cell transplantation. Antithymocyte globulins (ATG) are purified, concentrated preparations of polyclonal immunoglobulin G from hyperimmune serum of horses or rabbits immunized with human thymus lymphocytes. Both the horse and the rabbit products induce immunosuppression as a result of lymphocyte depletion and immune modulation. The exact mechanism of action is unknown but may include T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities. Both horse and rabbit ATG include multiple antibodies against T-cell surface antigens and have been used extensively in allog...
The pharmacokinetics of hemoglobin-based oxygen carrier hemoglobin glutamer-200 bovine in the horse. Hemoglobin-glutamer-200 (HBOC-200) is a hemoglobin (Hb)-based oxygen carrier (HBOC) comprising glutaraldehyde-polymerized bovine Hb. In this study, we sought to determine the pharmacokinetics of this first generation HBOC after IV infusion of 32.5 g of HBOC-200 solution in horses. Quantification of HBOC-200 in equine plasma and urine was performed using a method recently developed by our laboratory. The elimination from plasma was based on size distribution of the bovine Hb polymer. The decline of plasma concentration-time curve of HBOC-200 was described by a noninterchanging 2-compartmental m...
Urinary and serum concentrations of diclofenac after topical application to horses. The liposomal cream formulation of diclofenac, an NSAID, is an effective, safe, and convenient way to treat localized areas of inflammation in horses. The results of this study reveal urinary and serum concentrations of diclofenac following topical administration of 1% liposomal diclofenac cream for 10 days at the labeled dose and at 2X and 4X the labeled dose. These results demonstrate the slow absorption and elimination of 1% liposomal diclofenac cream and may be useful when estimating the withdrawal time needed before a competition in order to prevent an inadvertent positive drug test.
The detection of modafinil and its major metabolite in equine urine by liquid chromatography/mass spectrometry. A method has been developed for the detection of modafinil and its major metabolite, modafinil acid, in equine urine by solid-phase extraction and positive ion electrospray ionisation liquid chromatography/mass spectrometry. The method has been applied to the analysis of equine urine samples obtained after the oral administration of modafinil. Modafinil acid was the major component in the urine, and was detected up to 4 days post-administration. Unchanged modafinil was present at substantially lower concentrations, and was detected for only 24 hours.
Protein folding in classical perspective: folding of horse cytochrome c. Proteins meet with the stipulations of Levinthal. Two test tube variants of ferrocytochrome c (ferrocyt c) whose thermodynamic stabilities are vastly different refold to the same global minimum under a given final native condition, and they do so quickly at rates that do not reflect a strong dependence on the thermodynamic driving force. The transition-state ensemble is more unfolded-like, and the folding barrier offered is energetically sizable. The experiments involve neutral- (pH 7) and alkaline ferrocyt c pH (12.7), whose aqueous stabilities are 18 (+/-0.3) and 3 (+/-0.5) kcal mol(-)(1), r...