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 ketoprofen in healthy horses and horses with acute synovitis. The pharmacokinetic properties of a single intravenous dose of ketoprofen (2.2 mg/kg) in plasma and synovial fluid were compared in four healthy animals and four horses with experimentally induced acute synovitis. Synovitis was induced by the injection of a 1% solution of sterile carrageenan into the left intercarpal joint. Ketoprofen was administered at the same time as carrageenan infection. The plasma disposition followed a biexponential equation or a two-compartment model in most horses. The plasma harmonic mean half-life in healthy horses (0.88 h) was longer than in horses with synovitis ...
Disposition kinetics and bioavailability of piperacillin and cephapirin in mares. The pharmacokinetics of piperacillin (430 mg/kg.b.wt.) and cephapirin (20 mg/kg.b.wt.) were investigated following a single intravenous and intramuscular injection in normal mares. The serum concentration-time curve following a single intravenous injection of both antibiotics obeyed a two-compartment open model. After intravenous dose, piperacillin and cephapirin were transferred from central to peripheral compartment (k12) with values 0.46 and 0.52 h-1, while their passages from peripheral to central compartment (k21) were equal to 0.56 and 0.49 h-1, respectively. The elimination half-lives [...
Determination of triamcinolone acetonide in equine serum and urine by liquid chromatography-atmospheric pressure ionization mass spectrometry. Urine and serum samples collected from four standard-bred mares after 30-mg intraarticular administrations of triamcinolone acetonide were analyzed using combined high-performance liquid chromatography-atmospheric pressure ionization mass spectrometry. Maximum triamcinolone acetonide concentrations of 32.3, 14.8, 24.3, and 29.4 ng/mL in the urine and 2.7, 1.9, 2.3, and 2.5 ng/mL in the serum samples were observed. The peak concentrations of the drug were detected approximately 22 h (urine) and 12 h (serum) after administration. The drug elimination profiles for both urine and serum are present...
Kinetic studies and production rate of melatonin in pony mares. The aims of the present study were to determine basic kinetic parameters and the nycthemeral production rate of melatonin in the horse. Seven pony mares were used for the kinetic studies. Five other pony mares were used under long and short days for the production rate studies. Melatonin was administered by intravenous, oral, and intragastric routes at different dose levels. The plasma melatonin clearance was 1.02 +/- 0.31 l.kg-1.h-1, and the volume of distribution was 0.89 +/- 0.53 l/kg for the 0.4 microgram/kg melatonin dose. The systemic availability after oral and intragastric administrati...
Proteoglycan metabolism of equine articular cartilage and its modulation by insulin-like growth factors. The effect of human recombinant insulin-like growth factor 1 (rhIGF-1) on proteoglycan (PG) metabolism of full thickness equine articular cartilage explants was investigated. PG synthesis was stimulated at all ages, but higher concentrations of rhIGF-1 were required for maximal stimulation of adult cartilage. There were no changes in the hydrodynamic size, electrophoretic heterogeneity or composition of proteoglycans isolated from rhIGF-1-stimulated cartilage. rhIGF-1 reduced the rate of turnover of both newly synthesized and endogenous proteoglycans in all ages of cartilage investigated. The ...
Pharmacokinetics of ketoprofen after multiple intravenous doses to mares. The pharmacokinetics and urinary excretion of ketoprofen in six healthy mares after the first and last of five daily intravenous doses of 2.2 mg of ketoprofen per kg body weight were investigated using a high-performance liquid chromatographic (HPLC) method for determining plasma and urinary ketoprofen concentrations. Plasma ketoprofen concentrations declined triexponentially after each dose with no significant differences in plasma concentrations or pharmacokinetic parameter values between the first and last doses. The harmonic mean of the terminal elimination half-life of ketoprofen after th...
Enantioselective glucuronidation and subsequent biliary excretion of carprofen in horses. Carprofen (CPF) enantiomers and their glucuronide conjugates (GLUC) were measured in plasma and bile of horses after IV administration of the racemic compound (0.7 mg/kg of body weight). The CPF was detectable in plasma for up to 72 hours after dosing, whereas GLUC appeared early (time for maximal plasma concentration, 1 hour) and was measurable transiently at low concentration (maximal plasma concentration, 0.5 microgram/ml). The enantiospecific plasma profiles indicated a clear predominance of R-CPF, whereas the stereoselectivity of the glucuronides favored S-GLUC. At 1, 2, and 12 hours afte...
Pharmacokinetics of trimethoprim/sulphachlorpyridazine in horses after oral, nasogastric and intravenous administration. In the present study, the pharmacokinetic parameters of a trimethoprim/sulphachlorpyridazine preparation following intravenous administration, administration by nasogastric tube and administration with concentrate were determined in the horse. Eight adult horses were dosed at 1 week intervals in a sequentially designed study at a dose of 5 mg/kg trimethoprim (TMP) and 25 mg/kg sulphachlorpyridazine (SCP) on all occasions. Plasma concentrations of both drugs were measured serially for 48 h. Pharmacokinetic parameters of clinical importance (distribution and elimination half-lives, clearance, bi...
[Demonstration of two trimethoprim/sulfonamide combinations in bronchoalveolar lavage fluid of horses and determination of blood levels]. Five healthy horses were given a sulfadoxine/trimethoprim combination (Borgal, Hoechst AG) i.v. on day 1. The next ten days the horses got once a day a sulfadimethoxine/trimethoprim combination orally (Trafigal, Hoechst AG). The doses were given as recommended. One horse received no medicaments for control. On each horse six bronchoalveolar lavages were performed. Blood samples were taken to calculate blood levels and elimination half lives. To determine the amount of substances in lavage fluid and plasma the high performance liquid chromatography (HPLC) was used. Regularly low quantities of s...
Pharmacokinetics of intravenously administration of prednisolone in the horse as determined by radioimmunoassay. A radioimmunoassay was developed for prednisolone using IgG purified from rabbit antiserum. The assay was employed to determine the pharmacokinetics of prednisolone following intravenous administration of 450 mg of prednisolone sodium succinate (Solu Delta Cortef) to five adult Thoroughbred horses. The RIA had a sensitivity of 2 ng/ml and was relatively specific. It had cross-reactivity with 21-deoxycortisol (83.3%) cortisol (27.8%), 11-beta-hydroxyprogesterone (39.2%) and 17-hydroxyprogesterone (50%). However, it did not cross-react with naturally occurring steroids (cholesterol, testosterone...
Absorption and dosage of theophylline in the horse after single and repeated administration of a microencapsulated preparation. The kinetics of 2 formulations of theophylline were studied in horses. In an initial cross-over study (Phase I) serum concentration-time curves were determined for granulated and microencapsulated theophylline after a single oral administration (5 mg/kg bwt). In Phase II microencapsulated theophylline was administered at 5 mg/kg bwt/12 h for 10 days at feeding time, as in normal clinical practice. Although no significant differences between the 2 preparations were found with respect to the main kinetic parameters, the microencapsulated form was more evenly and completely absorbed from the dige...
Disposition of human drug preparations in the horse. III. Orally administered alclofenac. Concentrations of the non-steroidal anti-inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi-compartmental model with two successive rate constants ka1 = 0.05 +/- 0.06 h-1 and ka2 = 0.06 +/- 0.01 h-1. Alclofenac half-lives t1/2 alpha and t1/2 beta were 1.0 +/- 0.8 h and 6.9 +/- 1.5 h, respectively. Maximal conc...
Pharmacokinetics of thiopentone in the horse. The pharmacokinetics of thiopentone sodium administered intravenously as a single dose (11 mg/kg) were studied in acepromazine pre-medicated horses and ponies in which anaesthesia was maintained with either halothane (Group 1) or isoflurane (Group 2). The results showed that the disposition kinetics of thiopentone in horses and ponies were best described by a three-compartment open model. In plasma, a very short initial distribution phase in both horses and ponies, half-life 1.4 +/- 1.2 min (mean +/- SD) and 1.3 +/- 0.7 min, respectively, was obtained, which was followed by a second comparativ...
Plasma disposition of amikacin and interactions with gastrointestinal microflora in Equidae following intravenous and oral administration. Amikacin was detectable (> 0.02 micrograms/ml) in plasma for 12 h in horses and donkeys and for 8 h in ponies following intravenous (i.v.) administration at a dose rate of 6 mg/kg bodyweight. The elimination half-life (harmonic mean) of amikacin was 2.8, 1.6 and 1.9 h in horses, ponies and donkeys, respectively, and the mean body clearance was relatively slow (45.2, 82.4 and 58.0 ml/h.kg, respectively). A suitable dosage interval for the i.v. administration of amikacin sulphate to horses, ponies and donkeys, at a dose rate of 6 mg/kg, would be every 8 h in horses, and every 6 h in ponies an...
The pharmacokinetics and pharmacodynamics of procainamide in horses after intravenous administration. Six horses were administered either 15 or 20 mg/kg body weight (b.w.) procainamide (PA) as an intravenous (i.v.) dose over 10 min. The plasma concentrations of PA and N-acetylprocainamide (NAPA) as well as the pharmacodynamic effect (prolongation of the QT interval) were monitored. The PA plasma concentrations could be described by a one-compartment model with a t1/2 of 3.49 +/- 0.61 h. The total body clearance of PA was 0.395 +/- 0.090 l/hr/kg and the volume of distribution was 1.93 +/- 0.27 l/kg. As observed after PA administration, NAPA (an active metabolite) had a t1/2 longer than PA of 6....
Oral bioavailability of pivampicillin in foals at different ages. The plasma disposition of ampicillin after intravenous administration at a dose rate of 15 mg/kg was studied in six healthy, 1-month-old foals. The oral bioavailability of pivampicillin was determined in the same foals at four ages, ranging from 11 days to 4 months. Pivampicillin was administered orally at a dose rate of 19.9 mg/kg, which is equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 12 hours after administration. After intravenous administration, the mean distribution and elimination half-lives of ampicillin were 0.121 and...
The transition from inhomogeneous to homogeneous kinetics in CO binding to myoglobin. Heme proteins react inhomogeneously with ligands at cryogenic temperatures and homogeneously at room temperature. We have identified and characterized a transition from inhomogeneous to homogeneous behavior at intermediate temperatures in the time dependence of CO binding to horse myoglobin. The turnover is attributed to a functionally important tertiary protein relaxation process during which the barrier increases dynamically. This is verified by a combination of theory and multipulse measurements. A likely biological significance of this effect is in the autocatalysis of the ligand release p...
Gastric emptying of solid, non-digestible, radiopaque markers in ponies. The gastric emptying of different forms of ingesta occurs by a variety of mechanisms and dysfunction may selectively affect different components of the gastric contents. A technique for assessing gastric emptying of solid, indigestible, radiopaque markers was developed. Emptying of these markers in four ponies was variable in both pattern and rate (half emptying time ranged from less than one hour to more than 24 hours). However, whereas in man physically similar markers appear to empty relatively rapidly when fasting but are delayed by a meal, no such delay was evident in these ponies. The ho...
Prolonged presence of isoxsuprine in equine serum after oral administration. 1. Isoxsuprine [1-(4-hydroxyphenyl)-2-(1-methyl-2-phenoxyethylamino)-1- propanol] serum concentrations after single- and multiple-dose administration to horse were investigated using immunoenzymatic ELISA, HPLC-UV and thermospray HPLC-MS methods. 2. Using HPLC-MS, isoxsuprine was detected up to 72 h after a single administration (1.2 mg/kg by gastric probe) and up to 96 h after the end of serial administration (1.2 mg/kg every 12 h for 7 days). 3. ELISA detected the drug up to 96 h after a single dose and up to 6 days after the end of prolonged administration. 4. Isoxsuprine is present in hors...
Measurement of gastric emptying of water in foals by impedance epigastrography. Impedance epigastrography was used to measure gastric emptying rates on two occasions in each of three foals. After smoothing of the raw data, emptying of water appeared to obey an exponential model. The mean emptying rate constant (SEM) was 0.171 +/- 0.038 min-1 (mean emptying half time 4.9 +/- 1.0 min).
Ampicillin and its congener prodrugs in the horse. Ampicillin is an antibiotic commonly administered to horses by both the intramuscular (i.m.) and the intravenous (i.v.) route. Its physicochemical properties restrict its absorption after oral administration and explain its rapid elimination from the body. To prolong the effects of ampicillin in the horse, attempts have been made to alter its elimination and absorption rates. The alteration of urinary pH did not change the plasma disposition of the antibiotic but when probenecid was administered concurrently with ampicillin, a significant reduction of total body clearance was achieved. Ampicil...
Effect of xylazine and ketamine on the pharmacokinetics of alfentanil during halothane anaesthesia. We measured plasma concentrations of alfentanil in two horses after three different randomly ordered treatments. Each horse received halothane in oxygen by mask followed by a bolus dose of alfentanil 60 micrograms kg-1 i.v., halothane in oxygen by mask followed by an i.v. alfentanil infusion for 120 min and xylazine and ketamine followed by halothane and a bolus dose of alfentanil 60 micrograms kg-1 i.v. Halothane was maintained at 1.05-1.07% end-tidal concentration with a PaCO2 of 6-7.3 kPa. The plasma concentration-time curves were similar after bolus and infusion doses of alfentanil with ha...
Concentration of ceftiofur metabolites in the plasma and lungs of horses following intramuscular treatment. Ceftiofur sodium, a broad spectrum cephalosporin antibiotic approved for veterinary use, is metabolized to desfuroylceftiofur which is conjugated to micro as well as macromolecules. Twelve horses, weighting 442-618 kg, were injected intramuscularly with a single dose of 2.2 mg ceftiofur/kg (1.0 mg/lb) body weight. Blood was collected at various intervals over 24 h after treatment. Three groups of four horses each were euthanized and lungs were collected at 1, 12, and 24 h after treatment. The concentration of desfuroylceftiofur and desfuroylceftiofur conjugates in the plasma and lungs was dete...
Kinetic evaluation of muscle damage during exercise by calculation of amount of creatine kinase released. To quantify the extent of muscle alteration during prolonged exercise, the release rate of creatine kinase (CK) from striated muscle was measured in six horses during a rest period (6 h) and during three exercise tests (15, 30, and 60 km) at a constant speed of 200 m/min. CK clearance was measured after intravenous bolus administration (150 U/kg) of a CK solution obtained from horse muscle. The CK steady-state volume of distribution was 0.059 +/- 0.0215 l/kg, the terminal half-life was 123 +/- 28 min, and the plasma clearance was 0.36 +/- 0.10 ml.kg-1 x min-1. After an intramuscular CK adminis...
Caffeine clearance in the horse. The pharmacokinetic properties of intravenously administered caffeine were studied in 10 horses using a commercially available automated enzyme immunoassay. The harmonic mean for the distribution half-life was 5.2 min (range 1.4-18.7). The harmonic mean for the elimination half-life was 10.18 h (range 6.82-20.92). The harmonic mean of the volume of distribution was 0.32 L/kg (range 0.22-0.53). There was no correlation between the dose of caffeine/kg body weight and the elimination half-life (Spearman's coefficient of rank correlation = 0.19).
Kinetics and haematological effects of erythropoietin in horses. A plasma kinetic study of erythropoietin (EPO) was carried out in 4 horses after subcutaneous administration (30 IU/kg bwt) of recombinant human erythropoietin (rhEPO). At standardized intervals for 48 h before injection and for 60 h post-administration, the EPO plasma levels were determined with an immunoradiometric assay based on a sandwich technique. The peak plasma concentration (30-113 mIU/ml) was observed after a delay ranging from 6 to 9 h post-administration and the drug levels reached a physiological value around 60 h following rhEPO injection. Moreover, reference values for plasma EP...