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Biomedical subjects

G D Koritz

Publications and source records attributed to G D Koritz.

At least 55 records · Page 3Linked to original sources
PubMed1985

Preliminary study of the pharmacokinetics and toxicopathy of deoxynivalenol (vomitoxin) in swine.

Study was made of the pharmacokinetics and toxicopathy of deoxynivalenol (DON, vomitoxin) given IV to swine. In the 24 hours after swine were given DON, clinical signs of vomiting, diarrhea, muscular weakness, tremors, and twilight coma were similar to those observed with other 12,13-epoxytrichothecenes. Hypoglycemia and pancreatic islet cell lesions were observed which indicated that DON-induced changes in intermediary metabolism may be an insidious aspect of DON intoxication. Histopathologic examination of all organ systems revealed pancreatic acinar and islet cell necrosis and mild lympholysis of the mesenteric lymph nodes. The renal excretion of DON was altered by IV infusion of saline solution. Pharmacokinetic findings may indicate that DON was both secreted and reabsorbed by the renal tubules. The half-life of DON ranged from 2.08 to 3.65 hours. Residues of DON were not found in skeletal muscle of swine at 24 hours after dosing.

Animal Feed↗
PubMed1985

Prednisolone succinate and prednisolone acetate in cattle: pharmacokinetics and action on the adrenal gland.

The pharmacokinetics of prednisolone were studied in a group of 6 cows given prednisolone 21-sodium succinate IV and IM (600 micrograms/kg of body weight expressed as prednisolone alcohol) and prednisolone acetate IM (600 micrograms/kg of body weight expressed as prednisolone alcohol). After IV administration of prednisolone 21-sodium succinate, the half-life of elimination was 3.6 +/- 1.177 hours. After IM administration of prednisolone 21-sodium succinate, absorption was rapid and complete. After IM administration of prednisolone acetate, absorption was very slow with an absorption half-life of 48 hours, but was still complete. Basal plasma hydrocortisone was about 7.5 ng/ml. After IV and IM administration of prednisolone 21-sodium succinate, plasma hydrocortisone returned to normal values within 48 hours. In contrast, after IM administration of prednisolone acetate, a long adrenal suppression lasting from 4 to 6 weeks was observed.

Adrenal Glands↗
PubMed1983

Pharmacokinetics of chloramphenicol in non-lactating cattle.

The pharmacokinetics and bioavailability of a formulation of chloramphenicol base in propylene glycol were determined following administration of single intravenous (i.v.) and subcutaneous (s.c.) 50 mg/kg doses of chloramphenicol to six non-lactating Holstein cows. Mean serum concentrations of chloramphenicol following i.v. administration of 50 mg/kg declined rapidly from a peak of greater than 100 micrograms/ml to 6.9 micrograms/ml at 12 h after administration. Serum concentrations were not detectable at 24 h after administration. The curve of serum concentrations vs time was characteristic of a two-compartment open model. Mean i.v. data gave a biological half-life of 4.3 h and a volume of distribution of the central compartment of 0.44 l/kg. Serum concentrations of chloramphenicol following s.c. administration of 50 mg/kg rose slowly to a broad peak near 20 micrograms/ml from 3 to 8 h after administration and then declined. These data were also analysed according to a two-compartment open model. The biological half-life was 4.2 h and the volume of distribution of the central compartment was 0.50 l/kg. Significant adverse reactions, including acute collapse, intravascular haemolysis and haemoglobinuria, were observed in cows when dosed i.v. Cows dosed s.c. exhibited local reactions at injection sites. The disadvantages of administration of 50 mg/kg doses of chloramphenicol base in propylene glycol appear to be significant and may outweight the potential advantages of parenteral use of the drug as presently formulated.

Animals↗
PubMed1983

Pharmacokinetic studies of theophylline in cats.

The pharmacokinetics of theophylline were determined in adult cats and the data were fitted to a two-compartment model. Single intravenous and multiple oral doses of aminophylline were used. The mean plasma theophylline half-life (t1/2) following the single intravenous dose was 7.8 h and the mean apparent specific volume of distribution (V'd(area] was 0.46 1/kg. The absorption half-life (t1/2ab) was 0.5 h and the bioavailability was 96% following oral administration. There was excellent agreement between the predicted and observed plasma theophylline concentrations following multiple oral doses.

Animals↗
PubMed1983

Pharmacokinetics of digoxin in cattle.

Digoxin was administered as a single intravenous injection of 22 micrograms/kg to six cattle. The resulting serum concentrations were fitted by both a bi- and tri-exponential equation with the latter providing the best fit to the data of a majority of the animals. The biological half-life of digoxin in cattle was found to be 7.8 h. This relatively short half-life in comparison to other animal species dictates that digoxin should be administered more frequently to cattle to provide therapeutic concentrations in serum without broad fluctuations in serum concentrations. Computer simulations of various intravenous dosage regimens suggested that a loading dose of 22 micrograms/kg followed by an infusion of 0.86 micrograms/kg/h would offer the greatest safety and efficacy in bovine patients.

Animals↗
PubMed1983

Pharmacokinetics of lidocaine and its active metabolites in dogs.

The pharmacokinetics of lidocaine in dogs were investigated following the intravenous and intramuscular administration of single doses of lidocaine hydrochloride. The mean elimination rate constant and the mean specific clearance determined for the intravenous portion of the study were 0.786 h-1 and 2.40 1/kg/h, respectively. Following intramuscular administration the mean absorption rate constant was 7.74 h-1. Absorption was nearly complete as the percentage of an intramuscular dose absorbed averaged 91.9%. Concentrations of two N-deethylated metabolites, determined following the administration of lidocaine suggest that monoethylglycinexylidide is eliminated rapidly while glycinexylidide is more slowly eliminated. The relative contribution of these metabolites to the therapeutic and toxic effects of lidocaine and the potential for glycinexylidide accumulation during lidocaine administration remain to be investigated.

Animals↗
PubMed1983

Distribution of oxytetracycline in the healthy and diseased postpartum genital tract of cows.

Previously determined pharmacokinetic parameters of the disposition of oxytetracycline (OTC) in cows were used to predict an IV priming dose and a rate of constant IV infusion of OTC sufficient to approach steady-state equilibrium of the drug between plasma and genital tissue concentrations in healthy postpartum cows and postpartum cows with endometritis. After 8 hours' constant IV infusion at rates calculated to maintain a plasma concentration of approximately 5 micrograms/ml, the mean concentrations of OTC in plasma (microgram/ml) and tissues (microgram/g) of healthy and infected postpartum cows, respectively, were: plasma, 4.95 and 5.23; uterine tissue, 3.65 and 4.18; and ovarian tissue, 4.57 and 4.53. The mean plasma to genital tissue ratios for healthy and infected postpartum cows, respectively, were 1.38 and 1.31 for uterine tissue and 1.09 and 1.16 for ovarian tissue. There were no significant differences (P greater than 0.28) between healthy and infected postpartum cows in any of the parameters investigated. However, plasma-to-genital tissue ratios of concentrations of OTC in postpartum cows as a group were significantly higher (P less than or equal to 0.03) than those previously determined in cycling cows. Computer-simulated uterine tissue concentrations of OTC, after twice daily IV doses of 11 mg of OTC/kg of body weight, indicated that this dosage regimen would provide postpartum uterine tissue concentrations greater than 5 micrograms/g during most of the dosage interval.

Animals↗
PubMed1983

Distribution of oxytetracycline in genital tract tissues of postpartum cows given the drug by intravenous and intrauterine routes.

Oxytetracycline (OTC) was administered by constant IV infusion to 3 healthy postpartum cows at rates predicted to approach a steady-state plasma concentration of 5 micrograms/ml. After 8 hours of constant IV infusion, genital tissues were surgically removed. The mean plasma-to-tissue ratios of concentrations of OTC were 0.95, 1.33, 1.88, and 1.04 (2 cows only) for caruncles, endometrium, uterine wall, and ovaries, respectively. Differences between the ratios of any 2 of the uterine tissues were statistically significant (P less than 0.05). Intrauterine (IU) infusions of 5.5 mg of OTC/kg were administered to 3 healthy postpartum cows and 3 postpartum cows with metritis. The mean values of the fraction of the drug absorbed from the uteri of cows given IU infusions of OTC were 0.50 and 0.23 for healthy postpartum cows and postpartum cows with metritis, respectively. Concentrations of OTC were high in the caruncles and endometrium of all cows at 24 hours after IU infusions of the drug. Concentrations in the plasma, uterine wall, and ovaries were low, with mean concentrations of OTC in these tissues in postpartum cows with metritis being lower than those in the same tissues of healthy postpartum cows. Computer-simulated genital tissue concentrations of OTC after twice daily IV doses of 11 mg/kg indicated that this dosage regimen would provide postpartum uterine tissue concentrations greater than 5 micrograms/g throughout the dosage interval in all tissues, except the uterine wall.

Absorption↗
PubMed1982

Disposition of sulfadimethoxine in swine: inclusion of protein binding factors in a pharmacokinetic model.

Sulfadimethoxine was administered intravenously and orally to five swine. More than 75% of the dose was excreted into urine as the acetyl metabolite with 4-6% excreted unchanged. Plasma and urine data were not consistent when a linear pharmacokinetic model was used to describe the data. Sulfadimethoxine has a high affinity for plasma protein, and the data were subsequently fitted to a nonlinear model, which included saturable protein binding. The choice of a nonlinear model was further supported by a minimum value for the Akaike information criteria. The protein binding constant obtained was 2.8 X 10(4) M-1 and the total protein binding site concentration in plasma was 4.6 X 10(-4) M. Both values are comparable with in vitro data. This result suggests that the nonlinear model involving protein binding can be successfully applied to pharmacokinetic data. The apparent biological half-life of sulfadimethoxine (free and bound) in plasma was 14 hr; however, the half-life of elimination of free drug was 1.25 hr. Following oral administration, all of the dose was absorbed with an apparent absorption half-life of 2.9 hr.

Animals↗
PubMed1982

Distribution of oxytetracycline in the genital tract of cows.

Pharmacokinetic parameters of the disposition of oxytetracycline (OTC) were investigated in healthy cycling dairy cows after a single IV dose of 22 mg/kg of body weight. The biological half-life of OTC was 6.5 hours. These data were used to predict an IV priming dose and a rate of constant IV infusion of OTC sufficient to approach steady-state equilibrium of the drug between a plasma concentration of approximately 5 microgram/ml and a uterine tissue concentration. After 8 hours' constant IV infusion, the mean plasma concentration of OTC was 4.86 +/- 0.68 microgram/ml and the mean uterine tissue concentration of OTC was 4.50 +/- 0.45 microgram/ml. The mean ratio of plasma-to-uterine tissue OTC concentrations was 1.08. Computer-stimulated IV multiple doses of OTC at 11 mg/kg every 12 hours and 11 mg/kg every 24 hours suggested that the former dosage regimen could provide uterine tissue concentrations greater than 5 microgram/ml during the dosage interval, whereas the latter could provide such concentrations for only the first 12 hours of a 24-hour dosage interval.

Animals↗
PubMed1982

Organ blood flow and distribution of cardiac output in nonanesthetized swine.

Organ blood flow and distribution of cardiac output (CO) were determined in awake resting swine, using radionuclide-labeled 15-micrometer diameter microspheres. Absolute values of blood flow (per 100-g basis) were determined for various organs and peripheral tissues. Internal organs of the swine, which constituted 8.25 +/- 0.79% of the total body mass, received 45.46 +/- 2.64% of the resting CO. The fraction of CO received by brain, heart, kidneys, liver (via hepatic artery), and gastrointestinal tract was 1.13%, 3.04%, 12.95%, 4.27%, and 18.71%, respectively.

Animals↗
PubMed1982

Liver scintigraphy in ponies.

Six derivatives of ethylenediamine-N,N'-bis (alpha-2-hydroxy phenyl) acetic acid labeled with technetium 99m were prepared and their imaging qualities evaluated in ponies. The 6 agents produced good scintigraphic images of certain structures of the liver in the pony. For each agent, 13 different scans were taken. Dorsal views of the left lateral, right lateral, and quadrate lobe were obtained with dorsal scans. Left lateral and left lateral oblique (45 degrees) scans provided a left lateral view of the left lobe and a medial view of the right lateral lobe. Right lateral scans revealed the right lateral and quadrate lobes. Administration of 99mTc-labeled colloids which are commonly used in other species for liver scintigraphy resulted in extensive lung uptake in the pony.

Animals↗
PubMed1981

Disposition of sulfadimethoxine in cattle: inclusion of protein binding factors in a pharmacokinetic model.

Sulfadimethoxine was administered intravenously and orally to four cattle, and plasma and urine samples were collected at various times postdose. Modeling these data with a linear pharmacokinetic model gave unsatisfactory fits, and the data were subsequently fitted to a one-compartment model with saturable protein binding. The saturable protein binding model included the usual linear excretion and elimination processes as well as protein binding parameters. The values obtained in vivo for the binding constant, 5.01 x 10(4) M-1, and the total protein concentration, 7.89 x 10(-4) M, compared favorably with previously reported in vitro values. These results indicate that protein binding can be successfully included in a pharmacokinetic model.

Administration, Oral↗
PubMed1981

Pharmacokinetic studies of theophylline in dogs.

The pharmacokinetics of theophylline were investigated in dogs following intravenous, single oral, and multiple oral doses of aminophylline. Mean half-life (t1/2) of theophylline following single intravenous administration was 5.7 h and the apparent specific volume of distribution (V'd area) was 0.82 litre/kg. The bioavailability of theophylline was high (91%) following oral administration of aminophylline tablets and the absorption half-life (t1/2ab) was 0.4 h. Theophylline plasma concentrations observed following repeated oral administration of aminophylline tablets were somewhat greater than predicted. This suggests that theophylline plasma concentrations should be monitored and the dosage regimen individually adjusted in critically ill animals.

Animals↗
PubMed1981

Pharmacokinetics of theophylline in swine: a potential model for human drug bioavailability studies.

The pharmacokinetics of theophylline in swine were investigated following the oral and intravascular administration of single doses of theophylline free base. The mean half-life of theophylline following intravascular administration was 11.0 h, and the apparent specific volume of distribution was 0.61 liter/kg. Following oral administration, theophylline in solution was absorbed quite rapidly with a bioavailability of 79%. The similarity of the pharmacokinetics of theophylline in swine and humans suggests that swine may provide a useful model for the study of the bioequivalency of theophylline dosage forms intended for human use. The pharmacokinetic characteristics of theophylline also favor its consideration for usage as a therapeutic agent in swine.

Administration, Oral↗
PubMed1981

Sulfamethazine residues in swine.

Two possible causes of violative sulfonamide residues in swine were studied. To determine if sulfamethazine accumulated in the tissues of swine when the drug was administered in feed, the rates of plasma drug disappearance following a single oral dose and continuous feeding of the drug were compared. The rate of plasma drug disappearance was not significantly different (alpha = 0.05) when the two methods of drug dosing were compared. When feed containing 2 micrograms sulfamethazine/gm was fed to swine during a 7-day period preceding slaughter, the animal's liver contained violative residues. Violative concentrations of sulfamethazine were detected in the livers, kidneys, and skeletal muscle of swine which consumed feed containing 8 micrograms sulfamethazine/gm.

Animal Feed↗