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Biomedical subjects

J D Baggot

Publications and source records attributed to J D Baggot.

At least 55 records · Page 3Linked to original sources
PubMed1986

Distribution of kanamycin in ocular tissues of calves.

The ocular distribution of kanamycin following intramuscular, bulbar subconjunctival injection, or after constant rate intravenous infusion to calves was studied. Steady-state plasma concentrations of kanamycin were achieved in either normal calves, or in those experimentally infected with Moraxella bovis, and the concentrations of kanamycin in the serum, aqueous humor, vitreous body, tears, and the ocular tissues were measured. Kanamycin was not detected in the retina, lens, vitreous body, or the aqueous humor of any eyes, but the concentration of drug in the tears, conjunctiva, cornea and the orbital lacrimal gland of these calves ranged between 18 and 21% of that in serum. At steady-state plasma levels, the kanamycin concentrations in tears from eyes with keratoconjunctivitis and from normal eyes were similar. A study using lyophilized, powdered, ocular tissues in vitro showed that kanamycin was highly bound to the bovine retina and iris, and could be eluted using 0.2 N NaOH. The binding of kanamycin to other ocular tissues, including cornea, conjunctiva and lens, was significantly less. The concentration of kanamycin in the serum and the tears of calves was also measured after intramuscular or bulbar subconjunctival injection. After intramuscular administration of kanamycin (10 mg/kg of body-weight), the mean serum concentration was maximal at 1 h (32 micrograms/ml) and remained greater than or equal to 1.0 microgram/ml for 8 h. The mean tear concentration was maximal (3.1 micrograms/ml) at 30 min, and remained greater than or equal to 1.5 micrograms/ml for only 2.5 h. Following bulbar subjunctival administration of kanamycin (100 mg, single subconjunctival dose), the mean tear concentration was 1127 micrograms/ml at 30 min, less than or equal to 4.1 micrograms/ml at 4 h, and thereafter was less than or equal to 1.0 microgram/ml. It was concluded that kanamycin has limited distribution to the ocular tissues following parenteral administration. Binding of the drug to the ocular pigments may be responsible for its limited intraocular penetration.

Animals↗
PubMed1986

Influence of induced disease states on the disposition kinetics of imidocarb in goats.

The influence of fever, induced by different agents, on the disposition kinetics of imidocarb was determined in goats. Escherichia coli endotoxin (0.2 microgram/kg), Trypanosoma evansi (10(7) in 1 ml sterile glucose citrate), and Infectious Bovine Rhinotracheitis virus (10(6.5)TCID50) were the agents administered to induce the febrile state. In control and febrile animals the two-compartment model was used to describe the disposition kinetics of the drug. Fever caused significant changes to occur in the apparent volume of distribution and the body (systemic) clearance of imidocarb, but the half-life remained unchanged. The statistical significance of the changes in these pharmacokinetic parameters varied with the etiology of the febrile state. E. coli endotoxin and IBR virus caused corresponding decreases in apparent volume of distribution and clearance of imidocarb, while fever induced with T. evansi caused highly significant increases in both pharmacokinetic parameters. It was concluded that the alterations in the disposition kinetics of imidocarb that occurred in the febrile goats were related not only to the febrile reaction per se but also to the pathophysiology of the disease condition.

Animals↗
PubMed1986

Gentamicin dosage in foals aged one month and three months.

The absorption and disposition kinetics of gentamicin were compared at two dosage levels (2 and 4 mg/kg bodyweight [bwt]) in one- and three-month-old foals. Following intramuscular (im) injection of single 2 mg/kg bwt doses, the drug was absorbed rapidly and produced peak serum concentration (18.2 mu 5.3 +/- g/ml, n = 8) at 30 mins. Much wider variations were associated with the amount of drug absorbed and the serum gentamicin concentrations after administration at the higher dosage level. The half-life of gentamicin was similar in the one-month-old (3.7 +/- 1.7 h, n = 8) and three-month-old (3.3 +/- 0.8 h, n = 8) foals, and was independent of the dose. One-month-old foals did not appear to have a deficiency in renal excretion of gentamicin. The minimum inhibitory concentration of gentamicin for Corynebacterium equi and certain other equine bacterial isolates was less than 0.195 microgram/ml. It was concluded that 2 mg/kg bwt administered by im injection at 8 to 12 h intervals, depending on the severity of the infection, could be recommended as the dose rate for treatment of systemic infections caused by microorganisms that are susceptible to gentamicin.

Absorption↗
PubMed1986

Effect of short term starvation on disposition kinetics of chloramphenicol in goats.

The effect of short term starvation on the disposition kinetics of chloramphenicol was determined in goats. The same dosage level (10 mg kg-1) administered intravenously produced higher serum concentrations in the animals when they were starved than when they were not starved. This could be attributed to the significantly smaller (P less than 0.05) volume of the central compartment. Starvation significantly decreased the rate of elimination of chloramphenicol while the apparent volume of distribution of the drug was not altered. A significant decrease in the body clearance, 1.36 +/- 0.95 ml (min kg)-1 in the starved condition compared with 3.78 +/- 2.19 mg (min kg)-1 in the controls, caused a corresponding increase in the half life of chloramphenicol. The decreased rate of elimination was attributed to decreased hepatic microsomal metabolism since starvation did not change the fraction of the dose excreted unchanged in the urine. The clinical significance of the altered disposition of chloramphenicol is that administration at the usual dosing rate would lead to accumulation of the drug and eventual toxicity.

Animals↗
PubMed1986

Pharmacokinetics and endometrial tissue concentrations of ticarcillin given to the horse by intravenous and intrauterine routes.

Plasma and endometrial tissue concentrations of ticarcillin were measured in healthy mares. In the first of the 3 separate phases comprising the study, ticarcillin disodium (30 mg/kg) was administered IV. The mean peak concentration in endometrial tissue, 12.9 micrograms/g, was attained at 30 minutes. The plasma half-life of the drug in the 6 mares was 0.83 +/- 0.22 hour. Six grams of the drug was diluted in 250 ml of sodium chloride injection USP (2nd phase) and in 60 ml of sodium chloride injection USP (3rd phase). These dilutions were administered by intrauterine infusion. In phase 2, the mean peak concentrations of the drug in plasma and endometrium were 2.76 micrograms/ml and greater than 150 micrograms/g, respectively, at 60 minutes after it was administered. Endometrial concentrations greater than 150 micrograms of ticarcillin/g persisted through 2 hours after the drug was administered. Mean peak plasma and endometrial concentrations of the drug in phase 3 were 2.78 micrograms/ml and greater than 150 micrograms/g at 45 and 30 minutes after administration was done, respectively. At 1 hour after the drug was administered, endometrial concentrations of ticarcillin were significantly higher (P less than 0.01) after the drug was infused intrauterinely in the 250-ml volume than those after the 60-ml volume was infused. It was concluded that the volume of fluid in which the drug was infused into the uterus markedly influenced the duration of concentrations greater than 20 micrograms/g in endometrial tissue.

Animals↗
PubMed1985

Effects of ambient temperature on the half-life and dosage regimen of amikacin in the gopher snake.

Eight gopher snakes were given amikacin (5 mg/kg of body weight IM) and were housed at ambient temperatures of 25 C or 37 C. Snakes housed at 37 C had a larger volume of distribution, and a more rapid body clearance of amikacin while the apparent half-life was not changed significantly. The minimum inhibitory concentrations of amikacin against isolated snake pathogens were determined at both temperatures. Bacteria were twice as sensitive at 37 C than at 25 C. The data indicated that amikacin should be given IM at a dose schedule of 5 mg/kg (loading dose) followed by 2.5 mg/kg every 72 hours, and that snakes should be housed near the high end of their preferred optimum ambient temperature during treatment.

Amikacin↗
PubMed1985

Pharmacokinetics of pentobarbital and thiamylal as combined anesthetics in sheep.

This study was performed to investigate the possible mechanisms underlying prolongation of anesthesia times in sheep caused by the sequential administration of thiamylal and pentobarbital. Sodium thiamylal was injected as an intravenous bolus dose (13.2 mg/kg) followed in 7 min by sodium pentobarbital (14.3 mg/kg) by the same route to seven sheep. Separate studies were conducted for each of the two drugs administered separately to the same animals at the same doses. Mean anesthesia times (to the return of the palpebral reflex) were 7.89 min (thiamylal), 5.39 min (pentobarbital) and 34.1 min (the sequential combination). The kinetic parameters Vd(area), Vd(ss), t 1/2 beta, and ClB for either drug were not affected by the other when given in combination. The t 1/2 alpha was shorter, and the Vc was smaller, for pentobarbital when administered with thiamylal, while there were no changes in thiamylal disposition for the combination regimen. Computer-generated curves, associated with the two-compartment open model showing the fraction of dose in each compartment as a function of time, illustrated that pentobarbital rapidly achieved higher concentrations in the peripheral compartment after prior thiamylal administration. Protein-binding studies showed that this could not be attributed to displacement of pentobarbital from plasma albumin by thiamylal. Calculation of total and free drug concentrations at the time of awakening showed that, when the drugs were combined, the concentration of each drug was less than half of that observed at awakening when they were studied separately. It can be concluded that the prolonged sleeping times associated with the sequential combination of the two agents were not due to an alteration in kinetic parameters of either drug caused by the other, but rather to an additive effect of the subanesthetic concentrations of the two drugs when combined. The fact that sleeping times were supra-additive is attributed to a shift of awakening time from the distribution (alpha) phase, when given independently, to the elimination (beta) phase when administered in combination.

Anesthesia, Intravenous↗
PubMed1985

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, a suspension of cefadroxil monohydrate was administered intragastrically (25 mg/kg) to the same six horses. Plasma concentrations of the drug peaked at 1-2 h but, in general, absorption was both poor and inconsistent. The data were unsuitable for determination of cefadroxil bioavailability from this oral dosage form. Ninety-nine isolates of eleven bacterial species obtained from clinically ill horses were tested for susceptibility to cefadroxil. All strains of Streptococcus equi, Streptococcus zooepidemicus, coagulase-positive staphylococci, Corynebacterium pseudotuberculosis and five out of six strains of Actinobacillus suis were highly susceptible to the drug (MIC less than 4 micrograms/ml). Escherichia coli, Klebsiella pneumoniae and Salmonella sp. showed intermediate susceptibility (MIC 4-16 micrograms/ml), while all isolates of Corynebacterium (Rhodococcus) equi, Enterobacter cloacae and Pseudomonas aeruginosa proved to be highly resistant to cefadroxil (MIC greater than 128 micrograms/ml).

Animals↗
PubMed1985

Selection of an aminoglycoside antibiotic for administration to horses.

The serum concentrations of the aminoglycosides neomycin, kanamycin and streptomycin were determined after intravenous (iv) and intramuscular (im) administration. These values were then related to the minimum inhibitory concentrations (MIC) of a number of equine pathogenic bacteria to determine the duration of therapeutic serum concentrations of the aminoglycosides in the horse. Pharmacokinetic analysis of the data using neomycin as the example revealed a mean (+/- sd) peak serum concentration of 23.2 +/- 10.2 micrograms/ml present at 30 mins, and at 8 h the serum concentration was 2.8 +/- 0.8 micrograms/ml. From the pharmacological analysis of concentration-time data it was shown that neomycin was very rapidly absorbed from the im injection site, with an absorption half-time of 0.16 +/- 0.05 and was well absorbed (systemic availability was 73.7 +/- 26.9 per cent). A peak tissue level, which represented 40 per cent of the amount of drug in the body, was obtained at 32 mins after injection of the drug. At 8 h, the fractions of the dose in the central and peripheral compartments of the model were 1.5 per cent and 2.5 per cent respectively, and 96 per cent was the cumulative amount eliminated up to that time. Based on the MIC values of the majority of isolates of Corynebacterium equi, and only a few isolates of Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Streptococcus equi, one would expect a serum concentration of more than 2 micrograms neomycin/ml up to 8 h following im dosage (10 mg/kg) to be therapeutically effective.

Aminoglycosides↗
PubMed1985

Susceptibility of equine bacterial isolates to antimicrobial agents.

In vitro antimicrobic susceptibility patterns of commonly isolated aerobic gram-positive and gram-negative bacterial pathogens of equine origin were determined, using the agar-plate dilution method. All organisms were recent clinical isolates and included Corynebacterium (Rhodococcus) equi, Corynebacterium pseudotuberculosis, (coagulase positive) Staphylococcus sp, Streptococcus equi, Streptococcus zooepidemicus, Actinobacillus sp, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella. In vitro susceptibility levels were outlined for 14 antimicrobics as follows: amikacin less than or equal to 4.0 micrograms/ml, ampicillin less than or equal to 1.0 microgram/ml, amoxicillin less than or equal to 1.0 microgram/ml, cefadroxil less than or equal to 8.0 micrograms/ml, chloramphenicol less than or equal to 8.0 micrograms/ml, erythromycin less than or equal to 1.0 microgram/ml, gentamicin less than or equal to 2.0 micrograms/ml, kanamycin less than or equal to 4.0 micrograms/ml, penicillin less than or equal to 1.0 microgram/ml, tetracycline less than or equal to 1.0 microgram/ml, sulfadimethoxine less than or equal to 10.0 micrograms/ml, ormetoprim/sulfadimethoxine less than or equal to 0.5/9.5 micrograms/ml, sulfadiazine less than or equal to 10.0 micrograms/ml, and trimethoprim/sulfadiazine less than or equal to 0.5/9.5 micrograms/ml.

Aerobiosis↗
PubMed1985

Clinical pharmacokinetics of amikacin in dogs.

After IV, IM, and subcutaneous injection of single dosages of amikacin (5, 10, and 20 mg/kg of body weight) in each of 4 dogs, the elimination kinetics of amikacin were determined. The pattern of urinary excretion and cumulative amount excreted unchanged in 24 hours were also determined. Amikacin had a short half-life (approx 1 hour) that was independent of the dosage. Intravenous injection of 10 mg/kg gave apparent volume of distribution of 226 +/- 37 ml/kg and body clearance of 2.64 +/- 0.24 ml/min.kg (mean +/- SD, n = 4). Within 6 hours, greater than 90% of the antibiotic was excreted in the urine, regardless of the route of administration. For isolates of common bacterial species from the canine urinary tract, minimum inhibitory concentrations of amikacin, gentamicin, tobramycin, and kanamycin were determined in vitro. Cumulative percentages were approximately the same for urinary isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and coagulase-positive staphylococci that were susceptible (minimum inhibitory concentrations less than or equal to 32 micrograms/ml) to increasing concentrations of amikacin, gentamicin, and tobramycin, in vitro. Klebsiella pneumoniae was significantly more susceptible to amikacin than were the other bacteria evaluated. Widest variations in susceptibility to aminoglycosides were found with urinary isolates of streptococcal species. For dogs with normal renal function, an amikacin dosage of 10 mg/kg (IM or subcutaneously) is recommended every 8 hours for treatment of systemic infections, and every 12 hours for treatment of urinary tract infections caused by susceptible bacteria.

Amikacin↗
PubMed1985

Pharmacokinetics of gentamicin in the calf: developmental changes.

The purpose of this study was to determine the pharmacokinetic values for gentamicin in neonatal calves and to compare these values with those in adult cattle (cows). Gentamicin (4 mg/kg of body weight) was administered IV to 7 Holstein bull calves on days 1 (between 12 and 24 hours of age), 5, 10, and 15 after birth, and was administered once IV to 7 Holstein cows. Serum was collected from each animal before administration and at 22 different time intervals from 2 to 400 minutes after injection. Sera were analyzed for gentamicin concentrations. Decay of serum gentamicin concentrations was best described by a 2-compartment pharmacokinetic model. Elimination half-life (t1/2 (beta)) of gentamicin decreased from day 1 (149 minutes) to day 5 (119 minutes), but did not change between days 5 and 15 (111 minutes). Compared with the t1/2(beta) in 1- and 15-day-old calves, the t 1/2 (beta) in cows was shorter (76 minutes). In the calves, apparent volume of distribution (based on total area under the disposition curve) did not change between 1 (393 ml/kg) and 5 (413 ml/kg) days of age, decreased on day 10 (341 ml/kg) and cows day 15 (334 ml/kg), and was markedly smaller than that in cows (140 ml/kg). Total body clearance of gentamicin in cows (1.29 ml/min X kg) was lower than that seen in calves on day 1 (1.92 ml/min X kg) and on day 15 (2.10 ml/min X kg). The decrease in apparent volume of distribution of gentamicin was mirrored by a large decrease in the extracellular fluid volume, as measured by inulin space.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗