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Biomedical subjects

J D Baggot

Publications and source records attributed to J D Baggot.

At least 73 records · Page 4Linked to original sources
PubMed1984

Adverse effects of imidocarb dipropionate (Imizol) in a dog.

One of 13 healthy dogs used in a pharmacokinetic study of imidocarb dipropionate died due to difficulty in breathing, tachycardia, weakness and profuse diarrhoea. Autopsy findings showed marked pulmonary congestion and oedema. Kidneys were grossly enlarged and markedly congested with extensive haemorrhage in the cortex and medulla. Marked tubulonephrosis was also exhibited microscopically. Liver and spleen were moderately enlarged and congested. The adverse effects of imidocarb may be due to excessive acetylcholine action.

Acute Kidney Injury↗
PubMed1984

Effect of premedication with acetylpromazine on the disposition kinetics of thiopental.

This study was performed to determine whether premedication with acetylpromazine alters the disposition kinetics of thiopental in normal dogs. Based on nonlinear least squares regression analysis of the plasma concentration-time data obtained in individual dogs, a three-compartment open model was selected to describe the pharmacokinetic behavior of thiopental. While clinically premedication appears to delay time of awakening from thiopental anesthesia, statistical comparison (Student's t-test for paired data) of pharmacokinetic terms showed no significant difference. This may be largely attributed to wide individual variation in each parameter. The rate of change in volume of distribution at zero time (mean +/- SD, n = 7), which is a parameter that might have been expected to vary significantly, was 97 +/- 106 ml/min X kg for thiopental alone and 77 +/- 60 ml/min X kg following acetylpromazine premedication. Body clearance of thiopental was 1.96 +/- 0.59 ml/min X kg in dogs without premedication and 1.55 +/- 0.49 ml/min X kg following acetylpromazine. By relating observed time of awakening to plasma concentrations of thiopental it was determined that awakening from anesthesia occurred at a concentration of 20 micrograms/ml whether or not the dogs were premedicated. It can only be concluded that while premedication with acetylpromazine appears to delay time of awakening from anesthesia, it does not change the disposition kinetics of thiopental or affect the plasma concentration at the observed time of awakening.

Acepromazine↗
PubMed1984

Pharmacokinetics and bioavailability of theophylline in horses.

The pharmacokinetics and bioavailability of theophylline in horses were investigated following both intravenous and intragastric administration of aminophylline solutions at doses corresponding to 15 and 10 mg/kg theophylline base. A rapid distributive phase with a half-life of approximately 15-30 min was followed by a slower elimination half-life averaging 15-17 h. The apparent volume of distribution averaged 850-900 ml/kg. Theophylline, administered as aminophylline solution, was both rapidly and completely absorbed from the equine digestive tract. Based on the bioavailability and disposition kinetics of theophylline, an intragastric dosage regimen for aminophylline consisting of the administration of 5 mg/kg at 12 h intervals would be expected to maintain plasma theophylline concentrations within the therapeutic range.

Aminophylline↗
PubMed1984

Drug disposition in the neonatal animal, with particular reference to the foal.

Differences between neonatal and adult animals in their response to drugs can usually be attributed to altered disposition (ie, distribution, metabolism and excretion) processes during the neonatal period. These alterations affect the plasma concentrations as well as the concentrations of drug attained at the receptor site. Some characteristics of the neonatal period include greater absorption from the gastrointestinal tract, lower extent of plasma protein binding, increased apparent volume of distribution of drugs that distribute in extracellular fluid or total body water, increased permeability of the 'blood-brain' barrier and slower elimination of many drugs. The hepatic microsomal oxidative reactions and glucuronide conjugation are deficient metabolic pathways for a varying period of time, usually up to six weeks after birth or even longer in some species. Decreased metabolism can affect the duration of action of lipid-soluble drugs. Functional immaturity of the kidneys decreases the renal excretion of polar drugs and drug metabolites. Overall renal function appears to reach maturity within two weeks after birth in ruminant species and pigs, while maturation may take at least four weeks in other species of domestic animals. Considerable physiological and biochemical development takes place during the first five days after birth with maturation continuing more slowly over the succeeding five weeks. The time it takes for any process to reach functional maturity depends on the process in question and varies with the species of animal. The absorption, disposition and pharmacological response to drugs during the first 24 h after birth may be unique to that time and, because of lack of information, are impossible to predict.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1984

Influence of Escherichia coli endotoxin-induced fever on pharmacokinetics of imidocarb in dogs and goats.

The pharmacokinetics of imidocarb, administered as an IV bolus dose (4 mg/kg), was studied in normal and Escherichia coli endotoxin-induced febrile dogs and goats. In the febrile group, the drug was administered 1 hour after injection of the endotoxin. The plasma and urine concentrations of imidocarb were measured by spectrophotometry. The decline in plasma drug concentrations in both species was analyzed, using a 2-compartment open model. With the exception of the coefficient A and the volume of central compartment, E coli endotoxin-induced fever produced the same changes in kinetic determinants in both species. Fever significantly decreased the distribution rate constant in both dogs (P less than 0.05) and goats (P less than 0.01). The elimination rate constant and, in turn, the half-life were not altered by the endotoxin-induced fever in either species. The volume of distribution at steady-state was significantly lower (P less than 0.01) in the febrile dogs and goats. The body clearance of imidocarb was also significantly lower in the febrile dogs (P less than 0.05) and goats (P less than 0.01). The decreased apparent volume of distribution and lower body clearance of imidocarb could explain the higher plasma values of the drug in the febrile, compared with normal, animals.

Animals↗
PubMed1984

Dexamethasone and prednisolone in the horse: pharmacokinetics and action on the adrenal gland.

Pharmacokinetics of dexamethasone and prednisolone were studied in 6 horses given dexamethasone alcohol (IV or IM) or dexamethasone 21-isonicotinate as a solution IV or IM (50 micrograms/kg of body weight), prednisolone 21-sodium succinate IV or IM (0.6 mg/kg of body weight), or prednisolone acetate IM (0.6 mg/kg of body weight). Plasma concentrations were determined using a high-performance liquid chromatographic method. After dexamethasone alcohol (IV) or dexamethasone 21-isonicotinate (IV), the half-life of elimination was similar (53 minutes) for both formulations. After dexamethasone (alcohol and isonicotinate, IM), concentrations were low or nondetected. After prednisolone 21-sodium succinate (IV), the half-life of elimination (99.5 minutes) was significantly (P less than 0.01) longer than that for dexamethasone. After prednisolone 21-sodium succinate (IM), absorption was rapid and bioavailability was high. After prednisolone acetate (IM), absorption was slow and prednisolone was present in plasma for about 7 days. Due to the nonlinearity of prednisolone kinetics, a bioavailability higher than 100% was obtained. The basal plasma hydrocortisone concentration was approximately 70 ng/ml. After dexamethasone (IV or IM), plasma hydrocortisone values decreased after a 2-hour delay and returned to base line after a 3 to 4 day delay. After prednisolone 21-sodium succinate (IV or IM), plasma hydrocortisone decreased immediately (IV) or rapidly (IM) and returned to base line after a 24-hour delay. After prednisolone acetate (IM), plasma hydrocortisone decreased for up to 21 days.

Absorption↗
PubMed1983

Pharmacokinetics of imidocarb in normal dogs and goats.

The pharmacokinetics of imidocarb were studied in seven mongrel dogs and eight crossbred goats. An intravenous bolus dose (4 mg/kg) of 12% imidocarb dipropionate solution was injected into the cephalic vein in dogs and the jugular vein in goats. The plasma concentration of imidocarb was measured by spectrophotometry. The experimental data were analysed using a two-compartment open model. The apparent volume of the central compartment was significantly higher (P less than 0.01) in dogs than in goats. The significantly larger (P less than 0.05) apparent specific volume of distribution in goats than in dogs may be attributed to passive diffusion followed by ion trapping of the drug in rumen fluid. Neither the half-life nor body clearance differed significantly between dogs (t1/2, 207 +/- 45 min; ClB, 1.47 +/- 0.38 ml/min kg) and goats (t1/2, 251 +/- 94 min; ClB, 1.62 +/- 0.50 ml/min kg). While almost 80% of the dose had been eliminated at 8 h in both species, the high ratio of the imidocarb level in the peripheral-to-central compartment in goats suggests that a prolonged period may be required for complete elimination of the drug.

Animals↗
PubMed1983

Thiopentone pharmacokinetics and electrocorticogram pattern in sheep.

Thiopentone pharmacokinetics and electrocorticogram patterns were studied in a group of six sheep given thiopentone intravenously (20 mg/kg). Plasma concentrations were determined using a high-performance liquid chromatography method. A three-compartment open model was selected to describe the disposition kinetics of thiopentone. The drug had an apparent volume of distribution of 1005 +/- 196 ml/kg; body clearance was 3.5 +/- 0.8 ml/min-kg and the half-life, based on the slope of the terminal portion of the curve, was 196 +/- 64 min. From the electrocorticogram pattern, it seems likely that the highest concentrations in brain occurred between 47 and 217 sec after commencing administration and a brain penetration half-time of 26.5 +/- 2.87 sec was calculated. At the time of awakening (36.6 +/- 6.36 min) 24.1 +/- 6.3% of the dose was located in the central compartment, 12.6 +/- 8.2 was in the shallow peripheral compartment, 38.8 +/- 14.1 was in the deep peripheral compartment and 24.6 +/- 10.3 had been eliminated. Using simulated curves, it appeared that suppression of the shallow peripheral compartment (muscle) did not change the time of awakening; in contrast when elimination-rate constant was decreased, awakening was delayed. It was suggested that the relatively short duration of thiopentone anaesthesia in sheep should be attributed mainly to elimination of the drug by hepatic metabolism and uptake by body fat. This hypothesis, which differs from the widely accepted view that the duration of thiopentone anaesthesia is independent of the rate of hepatic metabolism, is discussed in terms of differences in regional blood flow between sheep and monogastric species.

Anesthesia, Intravenous↗
PubMed1982

Bioavailability of phenylbutazone preparations in the horse.

Plasma phenylbutazone concentrations were determined for up to 12 h in 6 horses following intravenous and oral phenylbutazone administration. To evaluate the bioavailability of different oral preparations, phenylbutazone was administered in a paste as well as the traditional powder form. The effect of the state of stomach contents on the absorption of phenylbutazone was investigated by administering the paste before and after feeding; the powder was given in a small bran mash and a full feed of lucerne chaff, wheaten chaff and bran. Despite great variability among individual horses both the paste form of phenylbutazone administered before a meal and the powder given in a small bran mash appeared to be almost completely absorbed, However, phenylbutazone paste administered after feeding or phenylbutazone powder given in a full feed resulted in lower peak plasma phenylbutazone levels than when administered on an empty or relatively empty stomach.

Administration, Oral↗
PubMed1981

The pharmacokinetics of thiopentone.

The pharmacokinetics of thiopentone was studied in six mongrel dogs using a high-performance liquid chromatographic method for measurement of the drug in the plasma. An intravenous bolus dose (20 mg/kg) of 2.5% thiopentone sodium solution was injected into the cephalic vein. While the two- and three-compartment models were used in the analysis of the experimental data, the disposition curve was adequately described by a biexponential equation. Plasma protein binding of thiopentone was determined in vitro using the equilibrium dialysis technique. The drug was bound to a moderately high extent (73.8 +/- 4.1%). The half-time of the initial phase, which comprises distribution/redistribution, was 14.9 +/- 3.3 mins. The apparent volume of distribution was quite high for an organic acid (843 +/- 194 ml/kg). This may be attributed to the high lipid solubility of the thiobarbiturate. The half-life was 6.99 +/- 2.18 h and a body clearance value of 1.51 +/- 0.60 ml/kg-min was obtained. It can be concluded from this study that the half-time of the distribution/redistribution phase approximates the duration of anaesthetic effect. Consequently, physiological conditions and disease states which influence distribution/redistribution rather than those affecting hepatic biotransformation of the drug are likely to affect anaesthesia.

Aging↗
PubMed1981

The pharmacokinetics of some aminoglycoside antibiotics in the horse.

The disposition kinetics and bioavailability of streptomycin, kanamycin and neomycin were determined following their administration as parenteral preparations to horses. Single doses (10 mg/kg) of each aminoglycoside were given by the intravenous (i.v.) and intramuscular (i.m.) routes and, at a later time, seven intramuscular doses were injected at 12-h intervals. The pharmacokinetic behaviour of the three aminoglycosides was similar, in that a rapid distribution phase was followed by a relatively short half-life. The half-life (mean +/- SD, n = 6) of kanamycin (1.80 +/- 0.17 h) was significantly (P less than 0.01; t test, 10 d.f.) shorter than that of streptomycin (3.40 +/- 0.42 h), while neomycin half-life (2.10 +/- 0.97 h) was of an intermediate length. The apparent volume of distribution of neither kanamycin nor neomycin varied significantly (P greater than 0.05) from that of streptomycin and numerically (V1 d congruent to 230 ml/kg) was the same as the extracellular fluid volume. The body clearance of kanamycin (88.5 +/- 11.3 ml/kg.h) was significantly (P less than 0.01) larger than that of streptomycin (47.5 +/- 7.9 ml/kg.h), while a significant difference in this parameter did not exist (P greater than 0.05) between neomycin and streptomycin. Following intramuscular injection, each aminoglycoside was rapidly and completely absorbed from the injection site, although neomycin showed wide individual variation in the fraction absorbed. The administration of multiple doses did not change either the bioavailability or the apparent half-life from the values obtained after a single dose. The only pharmacokinetic difference between these aminoglycosides that is of clinical importance lies in the rate of their elimination. A dosage interval of 8 h would be appropriate for kanamycin compared with a 12-h interval for streptomycin. The dosage interval for neomycin based on half-life should be 8 h but, due to the relatively greater toxicity of this aminoglycoside, an interval of 12 h might be recommended. The height of the peak serum concentration is determined by the size of the dose.

Aminoglycosides↗
PubMed1978

Pharmacokinetics and dosage of oxytetracycline in dogs.

The pharmacokinetics of oxytetracycline, which was given as a single intravenous dose (5 mg/kg), was studied in normal beagle dogs. Renal function was evaluated by the single injection technique and based on clearance of the radioiodine compounds 125I-iothalamate and 131I-iodohippurate. Values of GFR (4.42+/-0.77 ml/kg/min) and ERPF (12.91+/-1.49 ml/kg/min) showed normal renal function. The disposition curve describing decline of oxytetracycline activity in serum was described mathematically by a triexponential expression. Body clearance was 4.23+/-1.29 ml/kg/min. A dosage regimen (intravenous route of drug administration), based on overall elimincation rate constant (0.1155 h-1) and apparent specific volume of distribution (2 litre/kg), and consisting of a priming dose (10 mg/kg) followed by maintenance doses (7.5 mg/kg) at 12 h intervals was proposed. This dosage regimen was predicted to rapidly achieve and maintain steady state serum concentrations within the range 1.25 to 5.0 microgram/ml, which is therapeutic level for the majority of susceptible microorganisms.

Animals↗
PubMed1977

Pharmacokinetics of sulfadimethoxine in cats.

Pharmacokinetic parameters which describe distribution and elimination of sulfadimethoxine were determined in cats. Following intravenous administration of a single dose (55 mg/kg), disposition of the drug was described in terms of the biexponential expression: Cp = Ae-alphat + Be-betat. Based on total (free and bound) sulfonamide levels in the plasma, pseudodistribution equilibrium was slowly attained and the half-time of elimination (half-life) was 10.16 h +/- 2.50 (S.D., n = 6). Body clearance, which is the sum of all clearance processes, was 18.8 +/- 4.6 ml kg-1 h-1. Plasma protein binding, measured by equilibrium dialysis at sulfonamide concentration of 50 microgram/ml, was extensive (87.5% +/- 6.3, n =10). Computer-generated curves for an animal representative of the group, based on individual rate constants associated with the two-compartment open model, showed that 12% and 5% of the dose were present in the central and peripheral compartments, respectively, 24 h after administering the drug. A satisfactory dosage regimen might consist of a priming dose (55 mg/kg) and maintenance dosage (27.5 mg/kg at 24 h dosage intervals). Predicted plasma sulfadimethoxine concentrations would oscillate between 125 and 25 microgram/ml during the steady state. Influence of bacterial disease and febrile states on predicted levels remains to be verified experimentally.

Animals↗
PubMed1977

Application of pharmacokinetic methods to the drug residue profile.

A pharmacokinetic approach to the delineation of a drug residue profile in food-producing animals has been presented. It is recognized that the determination of a drug withdrawal period is one of the costly developmental procedures in drug development for food animals; thus it is believed that in the early developmental phases, a thorough pharmacokinetic characterization of a drug in the target species would greatly facilitate the design and quality of studies conducted in the later phases of new drug development. It is suggested that drugs that are intended for use in food animals can be characterized kinetically in less costly studies, the results of which might be used to determine the feasibility of developing a drug that might cause serious residue problems. It is also suggested that the pharmacokinetic modeling of a drug in the target animal may provide an essential data base for calculating dosage rates and intervals that directly relate to the efficacy aspects of drug development.

Animals↗
PubMed1977

A pharmacokinetic analysis of tylosin in the normal dog.

Studies were conducted to determine certain kinetic variables for tylosin in the normal dog. These variables were determined by pharmacokinetic analysis, measuring the decrease in serum concentration of tylosin activity in 3 separate experiments. Tylosin, given as a single intravenous dose of 10 mg of tylosin activity/kg of body weight, was calculated to have an elimination half life (t1/2beta) of 54 minutes and was no longer detectable in the serum by assay methods at about 270 minutes. In addition, tylosin appeared to be highly distributed with an apparent volume of distribution of about 1.7 L/kg and a tissue-to-plasma ratio of about 0.7. The body clearance of tylosin was calculated to be about 22 ml/kg minute. A separate multiple-dose intravenous experiment with the same dose per injection was conducted and showed similar results. Also, single intramuscular injection of 10 mg of tylosin activity/kg showed tylosin to peak after injection in the serum at 30 minutes, attaining a concentration of approximately 1.5 mug/ml. This concentration was maintained through 60 minutes and decreased slowly through 540 minutes. Data generated through 17 clinical cases indicated that the minimum inhibitory concentration for tylosin in Pasteurella spp tested was about 6.25 mcs/ml and for hemolytic Staphylococcus spp tested greater than or equal to 0.4 mug/ml. Thus, it would appear that tylosin, given at the recommended dose (6.6 to 11.0 mg tylosin activity/kg of body weight once or twice per day), would produce serum levels insufficient to treat all Pasteurella spp and some hemolytic Staphylococcus spp tested since a serum level of tylosin at slightly higher than 1 mug/ml for about 30 minutes was achieved in this study.

Animals↗
PubMed1977

Bioavailability, disposition kinetics and dosage of sulfadimethoxine in dogs--a correction.

A reevaluation of the disposition kinetics and extent of absorption of sulfadimethoxine in normal dogs following intravenous and oral dosage has been made. The tissue to plasma level ratio at the peak tissue level (k12/k21) was 0.55, while the tissue to plasma level ratio after distribution equilibrium (k12/k21-beta) was 0.926. The systemic availability of sulfadimethoxine from the oral suspension was 48.8% (24.4-86.2) when corrections for intrasubject variability were made.

Administration, Oral↗