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J W Blake

Publications and source records attributed to J W Blake.

50 records · Page 3Linked to original sources
PubMed1976

A review of the pharmacology, pharmacokinetics and behavioral effects of procaine in thoroughbred horses.

Since procaine has both local anaesthetic and central stimulant actions its presence in the blood or urine of racing horses is forbidden. After rapid intravenous injection of procaine HC1 (2.5 mg/Kg) in thoroughbred mares plasma levels of this drug fell rapidly (t 1/2 alpha = 5 min) and then more slowly (t 1/2 beta = 50.2 min). These kinetics were well fitted by a two compartment open model (Model I). This model gave an apparent Vdbeta for procaine in the horse of about 3,500 litres. Since procaine was about 45% bound to equine plasma protein this gives a true Vdbeta for procaine of about 6,500 litres. After subcutaneous injection of procaine HC1 (3.3 mg/Kg) plasma levels peaked at about 400 ng/ml and then declined with a half-life of about 75 minutes. These data were well fitted by Model I when this was modified to include simple first order absorption (K = 0.048 min-1) from the subcutaneous injection site (Model II). After intramuscular injection of procaine penicillin (33,000 I.U./Kg) plasma levels reached a peak at about 270 ng/ml and then declined with a half-life of about 9 hours. These data were approximately fitted by Model II assuming a first order rate constant for absorption of procaine of 0.0024 min-1. After intramuscular injection of procaine HC1 (10 mg/Kg) plasma levels of procaine peaked rapidly at about 600 ng/ml but thereafter declined slowly (+ 1/2 = 2 hours). A satisfactory pharmaco-kinetic model for this intramuscular data could not be developed. An approximation of these data was obtained by assuming the existence of two intramuscular drug compartments, one containing readily absorbable drug and the other poorly absorbable drug (Model III). After intra-articular administration of procaine (0.33 mg/Kg) plasma levels of this drug reached a peak at about 17 ng/ml and then declined with a half-life of about 2 hours. These data were not modelled.

Animals↗
PubMed1976

The gas-liquid chromatograph and the electron capture detection in equine drug testing.

Three gas-liquid chromatographic (G.L.C.) procedures discussed have been designed around the four "esses" of detection tests--speed, sensitivity, simplicity, and specificity. These techniques are admirably applicable to the very low plasma drug levels encountered in blood testing under pre-race conditions. The methods are equally applicable to post-race testing procedures, where both blood and urine samples are tested. Drugs can only rarely be detected by the electron capture detector (E.C.D.) without a prior derivatization step, which conveys to the drug(s) high electron affinity. Because of broad applicability, two derivatizing agents, heptafluorobutyric (HFBA) and pentafluorpropionic (PFPA) anhydrides are employed. The three techniques, allowing broad coverage of various drug classes are: 1) direct derivatization of drugs to form strongly electron capturing amides and esters. 2) reductive fragmentation of drugs with lithium aluminum hydride to form alcohols, with conversion to ester derivatives. 3) oxidative fragmentation of drugs with potassium dichromate to form derivatizable groups, followed by direct derivatization.

Animals↗
PubMed1976

Disposition kinetics of ketamine in the domestic cat.

The disposition kinetics and systemic availability of ketamine, a dissociative anaesthetic agent, was studied in normal domestic cats. A similar dose (25 mg/kg) of ketamine hydrochloride was administered by the i.v. and i.m. routes; drug concentrations in plasma were measured by a gas-liquid chromatographic procedure. A rapid distribution phase (t1/2 (alpha) = 3 min) was followed by a slower first-order elimination phase. The half-life of the drug (66.9 +/- 24.1 min) was independent of the route of parenteral administration. Absorption from i.m. site of administration was rapid, with peak plasma level at 10 min, and ca. 92 per cent of the dose was available systemically. Extent of plasma protein binding, measured in vitro at 5 and 20 mug/ml by equilibrium dialysis technique, was 53 per cent and independent of ketamine concentration. Simulated plasma and tissue level curves, which were generated by an analogue computer programmed with the individual rate constants of the two-compartment open model, showed that 10 and 15 per cent of the dose were present in the central and peripheral compartments, respectively, at 90 min after i.v. administration of the drug. Peak tissue level of 42 per cent of the dose was reached at 12 to 15 min. Parenteral administration of ketamine, at the dosage rate studied, quickly produced an immobilizing effect of variable duration (0.75 to 1.75 hr) in normal cats.

Animals↗
PubMed1976

Pharmacology of procaine in the horse: a preliminary report.

Rapid intravenous injection of 1 g of procaine hydrochloride in Thoroughbred mares produced variable signs of central nervous system excitation for as long as 4 minutes. Plasma concentrations of procaine were similarly variable and transient, decreasing with a half-life of approximately 25 minutes. In vitro, plasma from freshly collected equine blood hydrolyzed procaine with a half-life of approximately 7.5 minutes. This hydrolysis was apparently due to plasma esterases. Penicillin, when added free or complexed as procaine-penicillin, did not protect procaine against hydrolysis by these plasma esterases at pH 7.4.

Animals↗
PubMed1976

Drug interactions in the horse: effect of furosemide on plasma and urinary levels of phenylbutazone.

Horses pretreated with 6.6 mg/kg of phenylbutazone were injected with 1 mg/kg of furosemide intravenously. Furosemide had no clinically significant effect on either plasma levels or plasma half-life of phenylbutazone. Furosemide reduced urinary levels of phenylbutazone 18-fold to concentrations which may result in inconsistent drug detection in routine screening tests. The results show that it is not possible to monitor compliance with phenylbutazone medication rules by means of urinalysis alone if the use of furosemide is permitted. Furosemide treatment, however, does not interfere with monitoring by plasma level determinations.

Animals↗
PubMed1976

Pine oil toxicity in the horse: drug detection, residues and pathological changes.

This report concerns the detection and acute toxicity of pine oil (a commercially available disinfectant) after intravenous administration in horses. alpha Terpineol was identified as a major constituent of pine oil. alpha Terpineol was recovered from equine tissues by extraction into heptane and detected by gas chromatography, using either flame ionization detection or pentafluoropropionic anhydride derivatization and electron capture detection. After intravenous injection of 0.1 ml/kg, death due to massive pulmonary edema occurred within minutes. In this animal blood and tissue levels of alpha-terpineol of between 150 and 300 ppm were observed. After smaller doses of pine oil (0.033 ml/kg), horses survived until euthanized up to 48 hours later. Blood levels of alpha-terpineol became undetectable in one of these animals after 2 hours, and no tissue levels were detected at postmortem. Marked histopathological changes were seen in the lungs of animals which survived the initial injection period. It appears that after intravenous injection of pine oil in horses lesions are largely related to the respiratory tract, and the mechanism of death is acute pulmonary edema.

Animals↗
PubMed1976

Pharmacology of procaine in the horse: procaine esterase properties of equine plasma and synovial fluid.

Procaine added to whole equine blood or diluted plasma was hydrolyzed with half times of approximately 9 and 12 minutes, respectively, at 37 C. This hydrolytic activity was sensitive to heating and physostigmine, but did not affect procainamide. At pharmacologic concentrations of procaine, the rate of the hydrolytic reaction depended directly on the concentrations of plasma or procaine in the system and was less in whole blood than in plasma. These properties are consistent with hydrolysis being due to plasma esterases operating at less than saturating procaine concentrations. These esterases were also inhibited cooling, sodium fluoride, or arsenite. Synovial fluid had approximately 20% of the procaine esterase activity of plasma. Comparison of hydrolytic activities of plasmas from Thoroughbred, Standardbred, and other breeds of horses showed statistically significant differences in the rates at which individual plasmas hydrolyzed procaine. A frequency distribution of these rates showed unimodal distribution, indicating that all horses tested may be regarded as members of a single population.

Animals↗
PubMed1976

Electron capture detection of an apomorphine heptafluorobutyrate derivative at low picogram levels.

An electron capturing derivative of apomorphine was prepared by incubating the drug with heptafluorobutyric anhydride (HFBA), triethylamine and heat. Mass spectral analysis suggests that HFBA reacts with both phenolic hydroxyl groups on apomorphine to give a derivative detectable at low picogram levels. This method is sufficiently sensitive for pharmacokinetic studies in the horse and is likely applicable to other dopaminergic analogues of apomorphine.

Animals↗
PubMedDate not supplied

Immunoassay detection of drugs in racing horses: detection of ethacrynic acid and bumetanide in equine urine by ELISA.

We have raised antibodies and developed one-step enzyme-linked immunosorbent assays (ELISA) for the diuretics ethacrynic acid and bumetanide as part of a panel of pre- and post-race tests for high potency drugs in racing horses. These ELISA tests are rapid (completed within one hour), sensitive, and can be read by eye. The ELISA detects ethacrynic acid at a drug concentration for half-maximal inhibition (I-50) of about 2.5 ng/mL for the parent drug. After dosing horses intravenously with 5 mg ethacrynic acid per horse, the parent drug or its metabolites are detectable in urine for at least 8 hours. The bumetanide ELISA has an I-50 for the parent drug of about 2.0 ng/mL and will detect bumetanide or its metabolites for about 8 hours in urine after intravenous administration of a 1.7-mg dose per horse. Both antibodies are relatively specific for each drug and do not cross-react with other commonly used diuretics or other acidic compounds often found in post-race equine urine samples. Ethacrynic acid and bumetanide are potent diuretics suspected of being illegally substituted for furosemide in certain racing jurisdictions. Development of these rapid, sensitive, and simple tests for these agents will allow more effective pre- and post-race control of the use of these agents in racing horses. Both tests have recently uncovered several "positives" for these medications in a midwestern racing jurisdiction.

Animals↗
PubMedDate not supplied

The pharmacokinetics, plasma protein binding and time response relationships of 2-amino-5-phenyl-2-oxazolin-4-one (pemoline) in the horse.

The disposition kinetics of pemoline after iv and oral administration of 2.4 mg/kg of the drug were studied. The elimination half-life was 39.4 hr. The mean volume of distribution was 1.5 liters/kg indicating extensive tissue distribution and sequestration for an amphoteric drug. Plasma protein binding determined by in vitro equilibrium dialysis was concentration dependent. The mean binding capacity was found to be 0.80 mu-mol/g, an apparent dissociation constant of 3.73 X 10(-5) molar, and a total plasma protein concentration of 64.7 g/liter. The mean systemic availability by oral administration was 84.8% with an absorption half-time of 4.9 hr. The time course relationship showed that locomotor activity was directly related to the doses studied.

Administration, Oral↗
PubMedDate not supplied

The pharmacology of furosemide in the horse. V. Pharmacokinetics and blood levels of furosemide after intravenous administration.

Studies were undertaken to determine blood levels of furosemide in horses after 0.5- and 1.0-mg/kg doses administered iv. Analyses indicated that the pharmacokinetic parameters were dose independent and best described by a three-compartment open model. The alpha-, beta-, and gamma-phase half-lives of 5.6, 22.3, and 158.5 min, respectively, were observed after the 0.5-mg/kg dose. Similarly, the respective half-lives after the 1.0-mg/kg dose were 5.8, 24.1, and 177.2 min. After a 0.5-mg/kg dose of furosemide, population frequency distributions were evaluated at 1 hr and 4 hr post-drug administration. At 1 hr after dosing, the blood levels of furosemide in 30 horses were normally distributed. The mean plasma level was 97.9 ng/ml with a range of 41.9 ng/ml to 155.8 ng/ml and a SD of 25.0 ng/ml. Analyses of blood levels of furosemide in 47 horses at 4 hr after drug administration indicated that the population distribution was better fit by a normal curve after log transformation of the values. The mean plasma level at 4 hr post-dosing was 9.6 ng/ml with a range of 4.0 ng/ml to 19.4 ng/ml and a SD of 3.1 ng/ml. Based on this population distribution of the plasma levels, the probability of finding furosemide plasma concentrations above 24.6 ng/ml at 4 hr after anti-epistaxis dose was estimated at less than 1 in 1000.

Animals↗