Topic:Absorption
Absorption in horses refers to the process by which drugs and nutrients are taken up from the gastrointestinal tract into the bloodstream. This page compiles peer-reviewed research that examines the mechanisms underlying uptake, bioavailability, and the factors influencing absorption rates in horses. The studies explore pharmacokinetic profiles, the impact of different formulations, and how physiological conditions affect dietary absorption.
Fexofenadine in horses: pharmacokinetics, pharmacodynamics and effect of ivermectin pretreatment. The pharmacokinetics and the effects on inhibition of histamine-induced cutaneous wheal formation of the histamine H1-antagonist fexofenadine were studied in horse. The effect of ivermectin pretreatment on the pharmacokinetics of fexofenadine was also examined. After intravenous infusion of fexofenadine at 0.7 mg/kg bw the mean terminal half-life was 2.4 h (range: 2.0-2.7 h), the apparent volume of distribution 0.8 L/kg (0.5-0.9 L/kg), and the total body clearance 0.8 L/h/kg (0.6-1.2 L/h/kg). After oral administration of fexofenadine at 10 mg/kg bw bioavailability was 2.6% (1.9-2.9%). Ivermect...
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...
Effect of withholding macromolecules on the duration of intestinal permeability to colostral IgG in foals. To quantify absorption of colostral IgG by healthy neonatal foals and to test the hypothesis that delayed ingestion of macromolecules prolongs the duration of intestinal permeability to immunoglobulins (Ig) in newborn foals. Methods: Thirteen mixed breed foals. Methods: Foals were randomly assigned to two treatment groups, which were fed either a glucose-electrolyte solution or a commercial milk replacer for 12 h after birth, before being fed a known amount of colostral IgG. A control group was fed a known amount of colostral IgG from birth. The efficiency of IgG absorption was calculated foll...
Macronutrient digestibility, nitrogen balance, plasma indicators of protein metabolism and mineral absorption in horses fed a ration rich in sugar beet pulp. In a cross-over study with six mature horses, the effect of iso-energetic replacement of dietary glucose by beet pulp on macronutrient digestibility, nitrogen metabolism and mineral absorption was studied. The test ration contained 25% beet pulp in the total dietary dry matter. Beet pulp feeding significantly lowered crude fat and non-structural carbohydrate digestibility, but had no significant effect on digestibility of other macronutrients, faecal and urinary nitrogen excretion and the faecal to urinary nitrogen excretion quotient. However, on the beet pulp diet, plasma ammonia and creatini...
Disposition of flunixin meglumine injectable preparation administered orally to healthy horses. An injectable preparation of flunixin meglumine was administered orally and intravenously at a dose of 1.1 mg/kg to six healthy adult horses in a cross-over design. Flunixin meglumine was detected in plasma within 15 min of administration and peak plasma concentrations were observed 45-60 min after oral administration. Mean bioavailability of the oral drug was 71.9 +/- 26.0%, with an absorption half-life of 0.76 h. The apparent elimination half-life after oral administration was 2.4 h. The injectable preparation of flunixin meglumine is suitable for oral administration to horses.
Fenbendazole pharmacokinetics, metabolism, and potentiation in horses. The present study was designed to describe the pharmacokinetics and fecal excretion of fenbendazole (FBZ) and fenbendazole sulphoxide (FBZSO) and their metabolites in horses, to investigate the effects which concurrent feeding has on the absorption and pharmacokinetics of FBZ, and to determine the effect of coadministration of the metabolic inhibitor piperonyl-butoxide on the in vivo pharmacokinetics and in vitro liver microsomal metabolism of sulfide and sulfoxide benzimidazoles. The effect of piperonyl-butoxide on the enantiomeric genesis of the sulfoxide moiety was also investigated. Follow...
Evaluation of acetaminophen absorption in horses with experimentally induced delayed gastric emptying. To evaluate the correlation between the half-time of liquid-phase gastric emptying (T50) determined by use of nuclear scintigraphy, using technetiumTc 99m pentetate, and absorption variables of orally administered acetaminophen in horses with experimentally delayed gastric emptying. Methods: 6 mature horses. Methods: Delayed gastric emptying was induced by IV injection of atropine sulfate. Twenty minutes later, acetaminophen and technetium Tc 99m pentetate were administered simultaneously via nasogastric tube. Serial lateral images of the stomach region were obtained, using a gamma camera. Pow...
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...
Comparison of nuclear scintigraphy and acetaminophen absorption as a means of studying gastric emptying in horses. To evaluate the correlation between halftime of liquid-phase gastric emptying (T50), determined with nuclear scintigraphy using technetium Tc 99m pentetate, and absorption variables of orally administered acetaminophen. Methods: 6 mature horses. Methods: Technetium Tc 99m pentetate (10 mCi) and acetaminophen (20 mg/kg of body weight) were administered simultaneously in 200 ml of water. Serial left and right lateral images of the stomach region were obtained with a gamma camera, and T50 determined separately for counts obtained from the left side, the right side and the geometric mean. Power ex...
Metabolic functions of L-carnitine and its effects as feed additive in horses. A review. L-carnitine, a betaine derivative of beta-hydroxybutyrate, is found in virtually all cells of higher animals and also in some microorganisms and plants. In animals it is synthesized almost exclusively in the liver. Two essential amino acids, i.e., lysine and methionine serve as primary substrates for its biosynthesis. Also required for its synthesis are sufficient amounts of vitamin B6, nicotinic acids, vitamin C and folate. The first discovered ergogenic function of L-carnitine is the transfer of activated long-chain fatty acids across the inner mitochondrial membrane into the mitochondrial m...
Pharmacokinetics of cisapride in the horse. The purpose of this study was to determine the pharmacokinetics and absolute bioavailability of cisapride after intravenous (i.v.) and intragastric (i.g.) administration in healthy, adult horses. Five animals received single doses of 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg cisapride by the i.g. route in an open, randomized fashion on different occasions separated by a washout period of at least 48 h. Four of these horses were also given a single i.v. dose of 0.1 mg/kg cisapride. Jugular venous blood was collected periodically up to 24 h after dosing. Plasma cisapride concentrations were measured by...
Disposition of human drug preparations in the horse. VI. Tiaprofenic acid. Urinary and plasma concentrations of the nonsteroidal anti-inflammatory drug tiaprofenic acid were determined following oral and intramuscular administration of a dose of 1 g to five fasted horses. Quantitation was performed by high-performance liquid chromatography (HPLC). The limit of quantitation (LOQ) was 0.1 microg/ml and 0.5 microg/ml in 2 ml plasma and 1 ml urine, respectively. Assay precision and extraction recovery were between acceptable values. Tiaprofenic acid pharmacokinetics were described by non-compartment analysis of the data. Absorption was faster after oral administration as...
Pharmacokinetics of cisapride in horses after intravenous and rectal administration. To determine the i.v. pharmacokinetics of cisapride and measure systemic absorption after rectal administration. Methods: 5 healthy adult mares (380 to 610 kg). Methods: Cisapride was administered, i.v., at a dosage of 0.1 mg/kg of body weight. In the same horses, after a 1-week washout period, cisapride was administered rectally at a dosage of 1 mg/kg by mixing crushed tablets with propylene glycol and administering the mixture into the rectum. After each drug administration, a series of blood samples were collected. Plasma was obtained and analyzed by high-performance liquid chromatography t...
A myoglobin variant with a polar substitution in a conserved hydrophobic cluster in the heme binding pocket. Well-ordered internal amino acids can contribute significantly to the stability of proteins. To investigate the importance of the hydrophobic packing interface between helices G and H in the proximal heme pocket of horse heart myoglobin, the highly conserved amino acid, Leu104, was substituted with asparagine, a polar amino acid of similar size. The Leu104Asn mutant protein and its recombinant wild-type horse heart myoglobin counterpart were expressed from synthetic genes in Escherichia coli. Thermal denaturation of these two recombinant myoglobins, as studied by measurement of circular dichro...
Intramuscular bioavailability of ketoprofen lysine salt in horses. Lysine salts are often used in human pharmaceuticals to increase the solubility and absorption of acidic drugs when these are administered parenterally. In this study the intramuscular bioavailability of ketoprofen administered as the lysine salt was evaluated in horses (n = 5) treated intravenously and intramuscularly (2.2 mg/kg active substance) in a cross-over study. The absorption rate of ketoprofen administered as the lysine salt was rather low: the mean residence time increased from 31.7 min after IV injection to 128.9 min (after IM injection), and the bioavailability was high (mean 92.4...
Plasma pharmacokinetics of ranitidine HCl in adult horses. Plasma pharmacokinetics of ranitidine HCl were investigated after intravenous (i.v.) and oral (p.o.) administration of 2.2 mg/kg drug to six healthy adult horses. Concentrations of ranitidine were determined using normal-phase, high-performance liquid chromatography. Plasma concentrations of ranitidine HCl declined from a mean of 5175 ng/mL at 5 min to 37 ng/mL at 720 min after i.v. administration. A three-exponent equation, Cp = A1 x e-k1t + A2 x e-k2t + A3 x e-k3t, best described data for all horses. Mean values for model-independent values calculated from the last quantifiable time point we...
[The concentration changes of different phenylbutazone formulations in horse plasma]. In a study in the horse, the disposition, the pharmacokinetic parameters and the absorption rates of 3 formulations of phenylbutazone (injection solution, powder and paste suspension) have been determined. After i.v. injection, the half-life time of phenylbutazone has been determined to be 6.6-6.7 h. After oral administration, the absorption of phenylbutazone was found to be faster after administration via stomach tube than after direct application into the mouth. The absorption rat constant of the paste suspension was found to be higher than that of the powder (1.797-2.304 h-1 vs. 0.656-1.197...
Bioavailability of pivampicillin and ampicillin trihydrate administered as an oral paste in horses. Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses. Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only. The dose of pivampicillin was 19.9 mg/kg, and the dose of ampicillin trihydrate was 17 mg/kg. Both doses are equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 24 hours after administration. After administration of pivampicillin to starved and fed horses the...
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...
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...
Kinetic analysis of D-xylose absorption after its intragastric administration to mares deprived of food. Multicompartmental analysis was applied to study the kinetics of D-xylose distribution after its intragastric administration to healthy mares deprived of food for 12, 36, 72, and 96 hours. Disposition of D-xylose was described by a 5-compartment model. Maximal plasma D-xylose concentration was similar for 12 and 36 hours of food deprivation and was greater (P = 0.0001) than the values for 72 and 96 hours. Peak concentration of D-xylose appeared progressively later as food deprivation proceeded (P = 0.0001). Fractional rate of transfer (k1,6) was less after 96 hours of food deprivation, compare...
In vitro concentrative accumulation of D-xylose by jejunum from horses and rabbits. Accumulation of D-xylose by jejunal mucosa from healthy horses and rabbits was studied in vitro. When tissue sheets were incubated with 1 mM D-xylose for 60 minutes, mucosa from horses and rabbits accumulated D-xylose against a concentration gradient. There was no accumulation when equine specimens were incubated with 5 mM D-xylose. By comparison, equine jejunum accumulated D-glucose against a concentration gradient when incubated in 5 mM D-glucose. In equine and rabbit jejunum, 13.3 +/- 7.0% and 36 +/- 11.0%, respectively, of accumulated D-xylose was phosphorylated when sheets were incubated ...
Rifampin disposition in the horse: effects of age and method of oral administration. The effects of time and method of administration of rifampin with respect to feeding were evaluated in five mature horses. There was a significant (P less than or equal to 0.05) delay in time of maximum serum concentration and an apparent but not significant decrease in oral absorption when rifampin was given as a top dressing on grain as compared with administration in corn syrup 2 h before or 2 h after feeding. Although there were no differences between administration before or after feeding, administration 2 h prior to feeding was selected as the method of choice for future experiments. The...
Bioavailability and bioequivalence of veterinary drug dosage forms, with particular reference to horses: an overview. The route of administration and formulation of the dosage form affect the bioavailability (rate and extent of absorption) of a drug and may thereby influence the intensity and duration of the pharmacological effect. Location of injection site may affect the plasma concentration profile of drugs administered as aqueous suspensions or sustained release parenteral preparations (procaine penicillin G). When absorption influences the rate of elimination ('flip-flop' phenomenon), the apparent half-life of the drug will be increased (cefazolin sodium, i.m.; meclofenamic acid, p.o.). Absorption genera...
Influence of feeding schedule on the absorption of orally administered flunixin in the horse. The effects of access to hay and of restricted feeding on the pharmacokinetics of flunixin administered orally to six healthy ponies were compared in a cross-over study. No access to feed for a few hours before and after flunixin administration resulted in rapid absorption with a mean peak plasma concentration of 2.84 +/- 0.28 micrograms/ml attained in an average time of 0.76 +/- 0.18 h, followed by an exponential decline in plasma concentration. A lower peak plasma concentration was obtained when ponies had free access to hay before and after drug dosing. The mean maximum concentration (Cmax)...
Pharmacokinetics of tolfenamic acid in the horse. The pharmacokinetics of tolfenamic acid were studied in five ponies after an intravenous (iv) administration (2 mg/kg bodyweight [bwt]) and in four horses after an oral administration (30 mg/kg bwt) of tolfenamic acid. The plasma levels were determined by high pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). For the iv administration, a three-compartment model was used to represent the plasma concentration-time curve of the drug. The elimination half-life of the compound was 6.1 +/- 1.5 h, the total body clearance was 72.4 +/- 16.7 ml/kg bwt/h and the ste...
Evaluation of the oral vitamin E absorption test in horses. An oral vitamin E absorption test used in human beings was modified for use in horses. The most appropriate techniques with which to measure gastrointestinal tract absorption of vitamin E (alpha-tocopherol) in horses were developed. Vitamin E was administered orally, and serum values of alpha-tocopherol were measured by use of high-performance liquid chromatography at 0, 3, 6, 9, 12, and 24 hours after vitamin E administration. Variables included comparison of 2 dosages (45 and 90 IU/kg of body weight), routes of administration, and absorption dynamics of 3 preparations of dl-alpha-tocopherol....
Equipment for inhalation anesthesia. Inhalation anesthesia has three requirements: delivery of oxygen, delivery of an appropriate concentration of a volatile anesthetic agent, and removal of carbon dioxide. Halothane and isoflurane are the most commonly used anesthetic agents. They are usually delivered with a semiclosed circle system using an out-of-the-circuit vaporizer. Carbon dioxide is eliminated by chemical absorption and by flow of excess oxygen and waste anesthetic agent through the pop-off valve. These gases should be scavenged to prevent room contamination. A variety of ancillary equipment is available to assist the ane...