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Topic:Pharmacokinetics
Pharmacokinetics in horses involves the study of how drugs are absorbed, distributed, metabolized, and excreted in equine species. This field of study provides insights into the time course of drug concentrations within the horse's body and helps in understanding the effects of various pharmaceuticals. Key parameters in equine pharmacokinetics include absorption rates, bioavailability, half-life, and clearance. These parameters can vary significantly due to factors such as age, breed, and health status of the horse. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacokinetic profiles of different drugs in horses, aiming to optimize dosing regimens and improve therapeutic outcomes in equine medicine.
Isolation of meclofenamic acid and two metabolites from equine urine–a comparison between horse and man. Two metabolites of meclofenamic acid have been isolated from equine urine. Both metabolites are found to be monohydroxylated forms of meclofenamic acid by gas chromatography-mass spectrometry after extractive alkylation. The parent drug and the metabolites are separated by reversed-phase liquid chromatography on a Spherisorb ODS column, using methanol-phosphate buffer eluents and UV detection at 280 nm. The structure of the metabolites is discussed on the basis of LC, TLC and GC-MS data.
[14C]monensin balance in bile-fistulated ponies. To measure absorption of monensin or its metabolites and its elimination from the body, [14C]monensin sodium was given orally (1 mg/kg body wt) to two bile-fistulated ponies and iv (8.7 mg) to one bile-fistulated pony. For one orally-dosed pony, 4.7% of the 14C was eliminated in bile, 52% in feces, .7% in urine and 33% remained in the gastrointestinal (GI) tract after 3 d. Total 14C recovery was 90%. For the other orally-dosed pony, 18.3% of the 14C was eliminated in bile, 69% in feces, 1.7% in urine and 7% remained in the GI tract after 4 d. Total 14C recovery was 98%. For the iv-dosed pony, ...
Identification of betamethasone and a major metabolite in equine urine. Betamethasone and its major unconjugated metabolite, 6-beta-hydroxybetamethasone, were detected in equine urine by thin-layer chromatography and characterized by micro-liquid chromatography/mass spectrometry (micro-LC/MS). Their structures were confirmed by a combination of infrared spectroscopy and nuclear magnetic resonance spectroscopy.
Pharmacokinetics of probenecid and the effect of oral probenecid administration on the pharmacokinetics of cefazolin in mares. The pharmacokinetics and bioavailability of probenecid given IV and orally at the dosage level of 10 mg/kg of body weight to mares were investigated. Probenecid given IV was characterized by a rapid disposition phase with a mean half-life of 14.0 minutes and a subsequent slower elimination phase with a mean half-life of 87.8 minutes in 5 of 6 mares. In the remaining mare, a rapid disposition phase was not observed, and the half-life of the elimination phase was slower (172 minutes). The mean residence time of probenecid averaged 116 minutes for all 6 mares and 89.2 minutes for the 5 mares with...
Dose-related effects of ethylketazocine on nociception, behaviour and autonomic responses in the horse. Sensitive methods for measuring the analgesic, physiological and behavioural effects of opioids in the horse have recently been developed. Fentanyl, a prototypic mu-opiate receptor agonist, has been previously shown to produce a syndrome characterized by marked analgesia and locomotor stimulation as well as tachycardia, tachypnoea and behavioural arousal. To determine whether other opiate receptors mediate some of the actions of the narcotic analgesics in the horse, an agent with activity at kappa- and to lesser extent mu-receptors was studied using a vigorous experimental protocol. Like fenta...
Analysis of pharmaceutical dosage forms for oxfendazole: II. Simultaneous liquid chromatographic determination of oxfendazole and trichlorfon in equine paste. A reverse phase liquid chromatographic procedure is described for the simultaneous determination of oxfendazole [2-(methoxycarbonylamino)-5-phenylsulfinylbenzimidazole] and trichlorfon [(2,2,2-trichloro-1-hydroxyethyl)phosphonic acid dimethyl ester] in equine paste. The sample is extracted by sonication in methanol. Insoluble excipients are removed by centrifugation and an aliquot plus internal standard are diluted with dilution solvent (water-acetonitrile-phosphoric acid, 80 + 20 + 1). The samples are filtered and injected onto a Partisil-5 ODS-3 column with acetonitrile-0.01 M phosphate buff...
Rapid extraction, radioiodination, and in vivo catabolism of 125I-labeled fibrinogen in the horse. Two methods were analyzed for the rapid extraction of equine fibrinogen from fresh plasma, using ammonium sulfate-sodium phosphate buffer. Fibrinogen from each of these 2 methods was then radiolabeled with 125I (half-life = 60.2 days, gamma = 35 keV), using monochloroiodine reagent. Mean protein-bound activity was 98.5% and mean clottable radioactivity was 94.1%. Radiolabeled fibrinogen administered IV to 15 horses had an overall mean (+/- SD) plasma half-life of 4.95 +/- 0.44 days.
Effects of oral cimetidine on plasma concentrations of phenylbutazone in horses. Phenylbutazone was administered to six Thoroughbred horses in a cross-over study in which the horses received cimetidine pretreatment or no cimetidine pretreatment. Blood samples were collected at various times for 48 h after phenylbutazone administration and the plasma was analysed for phenylbutazone. Cimetidine pretreatment elevated phenylbutazone plasma concentrations during the first 8 h after phenylbutazone administration. The absorption rate, maximum phenylbutazone plasma concentrations and AUC were significantly greater with cimetidine pretreatment. The half-life of phenylbutazone did n...
Flunixin meglumine given in small doses: pharmacokinetics and prostaglandin inhibition in healthy horses. The pharmacokinetics and inhibition of prostaglandin synthesis in conscious horses given various dosages of flunixin meglumine were studied. Plasma concentrations of flunixin were measured by high-performance liquid chromatography, and serum thromboxane B2 and 6-keto prostaglandin F1 alpha were quantitated by radioimmunoassay. Within the dosage range studied, linear pharmacokinetics were achieved. After IV administration of flunixin (1.1 mg/kg, 0.25 mg/kg, 0.1 mg/kg), significant suppression of serum thromboxane generation persisted for 12, 4, and 3 hours, respectively. Repeated administration...
Quantitative methodology for corticosteroids based on chemical oxidation to electrophilic products for electron capture-negative chemical ionization using capillary gas chromatography-mass spectrometry. I. Assessment of feasibility in the analysis of horse urine for dexamethasone. Sensitive and specific methodology based on capillary column gas chromatography-electron capture-negative chemical ionization-mass spectrometry has been developed for the quantitative analysis of corticosteroids from biological fluids. The feasibility of this method is demonstrated in the quantitative analysis of dexamethasone in horse urine following administration of the drug. A structurally similar compound, 6 alpha-methylprednisolone, is added to the urine as an internal standard. The free dexamethasone and the internal standard are extracted and oxidized to high-electron-affinity 1,4-andr...
Theophylline and dyphylline pharmacokinetics in the horse. The pharmacokinetics of theophylline and dyphylline were determined after IV administration in horses. In a preliminary experiment, the usual human dosage (milligram per kilogram) of each drug was given to 1 horse. Results were used to calculate dosages for a cross-over study, using 6 horses for each drug. Theophylline plasma concentrations decreased triexponentially in 5 of 6 healthy horses after IV infusion of 10 mg of aminophylline/kg of body weight for 16 to 32 minutes. In the 6 horses, total body elimination rate constants were variable, and the half-life of theophylline was 9.7 to 19.3 h...
Hepatobiliary transport of indocyanine green and sulfobromophthalein in fed and fasted horses. Fasting is associated with unconjugated hyperbilirubinemia in several species, including the horse. Studies in ponies showed that a 3-day fast decreased plasma clearance of bilirubin, cholic acid, and sulfobromophthalein (BSP). Since these organic anions are conjugated with different substrates, it is possible that observed differences in plasma clearance result from a general decrease in hepatic conjugating capacity during the animals' fasting. To test this hypothesis, the effects of a 3-day fast on plasma clearance of IV injected BSP (4.4 to 5.1 mg/kg), which is conjugated to glutathione, an...
Inhibitory effects of intravenous chloramphenicol sodium succinate on the disposition of phenylbutazone in horses. The effects of i.v. chloramphenicol sodium succinate on the pharmacokinetics of i.v. phenylbutazone in six healthy adult horses were investigated. Administration of chloramphenicol sodium succinate to mares reduced mean (+/- SD) phenylbutazone clearance from 0.600 +/- 0.222 to 0.339 +/- 0.123 ml/min per kg and increased mean (+/- SD) half life from 244 +/- 59.8 to 371 +/- 80.8 min and mean residence time from 333 +/- 86.2 to 533 +/- 124 min. The mean steady-state volume of distribution of phenylbutazone was unchanged, with mean (+/- SD) values of 187 +/- 28.9 ml/kg in control animals and 170 +...
Pharmacokinetics and bioavailability of cephalothin in horse mares. The pharmacokinetics and bioavailability of cephalothin given to 6 horse mares at a dosage level of 11 mg/kg of body weight IV or IM were investigated. The disposition of cephalothin given IV was characterized by a rapid disposition phase with a mean half-life of 2.89 minutes and a subsequent slower elimination phase with a mean half-life of only 14.7 minutes. The mean residence time of cephalothin was 10.6 +/- 2.11 minutes. The total plasma clearance of cephalothin averaged 13.6 ml/min/kg and was caused by metabolism and renal elimination. Renal clearance of cephalothin averaged 1.32 ml/min/k...
Disposition of sulfadimidine and its N4-acetyl and hydroxy metabolites in horse plasma. The plasma disposition of sulfadimidine (SDM) and its metabolites N4-acetylsulfadimidine (N4-SDM), 6-hydroxymethyl-4-methyl-pyrimidine (SCH2OH) and 5-hydroxy-4,6-dimethyl-pyrimidine (SOH), was studied in three horses following intravenous administration of SDM at dose levels of 20 and 200 mg/kg in cross-over trials. The percentages of N4-SDM (0.58-0.90%), SOH (0.83-6.75%) and SCH2OH (0.38-0.71%) in plasma, expressed as a percentage of the total sulfonamide concentration, were small and their plasma concentrations were parallel with SDM from 4 h following administration. At high doses (200 mg/k...
Total intravenous anaesthesia in the horse with propofol. The use of propofol, solubilised in a non-ionic emulsifying agent, for the induction and maintenance of anaesthesia in experimental ponies was assessed. Pilot studies revealed that premedication with xylazine (0.5 mg/kg bodyweight [bwt]) intravenously (iv) followed by propofol (2.0 mg/kg bwt) iv provided a satisfactory smooth induction. Two infusion rates (0.15 mg/kg bwt/min and 0.2 mg/kg bwt/min) were compared for maintenance of anaesthesia. An infusion rate of 0.2 mg/kg/min produced adequate anaesthesia in these ponies. Cardiovascular changes included a decrease in arterial pressure and card...
Combined pharmacokinetics of gentamicin in pony mares after a single intravenous and intramuscular administration. Healthy mature pony mares (n = 6) were given a single dose of gentamicin (5 mg/kg of body weight) IV or IM 8 days apart. Venous blood samples were collected at 0, 5, 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 30, 36, 40, and 48 hours after IV injection of gentamicin, and at 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, and 30 hours after IM injection of gentamicin. Gentamicin serum concentration was determined by a liquid-phase radioimmunoassay. The combined data of IV and IM treatments were analyzed by a nonlinear least-square...
Cefadroxil in the horse: pharmacokinetics and in vitro antibacterial activity. Sodium cefadroxil was administered as a single intravenous dose (25 mg/kg) to six healthy adult mares. Plasma samples were collected over a 24-h period and cefadroxil concentrations were measured by microbiological assay. The pharmacokinetic behavior of the drug was appropriately described in terms of a one-compartment open model. Values for the major pharmacokinetic terms were: extrapolated initial plasma concentration = 59.2 +/- 15.0 micrograms/ml; half-life = 46 +/- 20 min; apparent volume of distribution = 462 +/- 191 ml/kg; and body clearance = 7.0 +/- 0.6 ml/min.kg. In a subsequent study...
[An undesirable drug interaction in horses? Complications which can occur during the administration of coumarin derivatives and phenylbutazone]. A study of the literature was done because of questions asked in a court of justice concerning possible poisoning in a jumper, resulting from administration of both phenylbutazone and a coumarin derivative within a particular period. In view of the mechanisms of action and the pharmacokinetic characteristics of the agents, these forms of combined treatment are also highly inadvisable in horses.
[The treatment of podotrochilosis with oral anticoagulants. An instruction insert desired]. The anticoagulant, warfarin, has been reported to be effective as treatment for navicular disease in horses. Since other forms of treatment for this disease are palliative, this new anticoagulant therapy has become widely employed. Despite the fact that initiation of anticoagulant therapy is relatively simple, attending veterinary practitioners should be aware that careful monitoring of this therapy is required for both safety and efficacy. Navicular disease is an example of equine thrombotic disease, and the goal of warfarin therapy is the prevention of new thrombus formation, while at the sa...
Pharmacokinetics of small doses of 3-methylindole given to horses. The pharmacokinetics of 3-methylindole (3MI) given orally in 2 doses (10 mg/kg and 20 mg/kg) to horses were determined. The pharmacokinetic plasma-concentration profiles for 3MI (10- and 20-mg/kg dosages) in horses were represented by a 2-compartment open model with first-order absorption, as determined by nonlinear least-squares regression analysis. Absorption of 3MI at both dosages was rapid. Comparisons of the peak plasma concentrations, the postdistribution half lives, total clearances, and areas under the curve of the plasma-concentration profiles between the 10- and the 20-mg/kg dosages ...
Pharmacology and pharmacokinetics of drugs used to treat cardiac disease in horses. The rational therapy of cardiovascular disease in horses requires a thorough knowledge of the pharmacology and pharmacokinetics of several specific drugs (digitalis, digoxin). Calcium solutions, dopamine, and dobutamine are frequently used to treat congestive heart failure in horses. Quinidine, procainamide, lidocaine, and propranolol are used to treat a variety of supraventricular and ventricular arrhythmias. Furosemide, a highly potent loop diuretic, is used to eliminate edema and promote diuresis. A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and pr...
Identification of metabolites of methylprednisolone in equine urine. Methylprednisolone and three metabolites, 17,21-dihydroxy-6 alpha-methyl-1,4-pregnadiene-3,11,20-trione, 6 alpha-methyl-17,20 beta,21-trihydroxy-1,4-pregnadiene-3,11-dione, and 6 alpha-methyl-11 beta,17,20 beta,21-tetrahydroxy-1,4-pregnadien-3-one were detected in equine urine after intraarticular administration of methylprednisolone acetate. All four compounds were excreted both in the unconjugated form and as glucuronic acid conjugates. They were identified by comparing data obtained from analyses by high performance liquid chromatography, thin-layer chromatography, ultraviolet spectroscopy ...
Quantitative determination of betamethasone and its major metabolite in equine urine by micro-liquid chromatography-mass spectrometry. Micro-liquid chromatography-mass spectrometry (micro-LC-MS) was utilized to quantitatively determine betamethasone and its major unconjugated metabolite, 6 beta-hydroxybetamethasone, in equine plasma and urine. The advantage of micro-LC-MS over conventional gas chromatography-mass spectrometry in corticosteroid determination is illustrated and the reliable, steadfast nature of micro-LC-MS is demonstrated through example.
