Diane F. Gerken

Inhibitory effects of intravenous chloramphenicol sodium succinate on the disposition of phenylbutazone in horses

The effects of i.v. chloramphenicol sodium succinate on the pharmacokinetics of i.v. phenylbutazone in six healthy adult horses were investigated. Administration of chloramphenicol sodium succinate to mares reduced mean (±SD) phenylbutazone clearance from 0.600±0.222 to 0.339±0.123 ml/min per kg and increased mean (±SD) half life from 244 ± 59.8 to 371 ± 80.8 min and mean residence time from 333 ± 86.2 to 533 ± 124 min. The mean steady-state volume of distribution of phenylbutazone was unchanged, with mean (±SD) values of 187 ± 28.9 ml/kg in control animals and 170 ± 32.4 ml/kg after chloramphenicol sodium succinate.

Clinical effects and plasma concentration determination after 2,4-dichlorophenoxyacetic acid 200 mg/kg administration in the dog

Objective: To investigate the clinical effects and to determine the 2,4-dichlorophenoxyacetic acid plasma concentrations after a dose of twice the reported LD50 (100 mg/kg) was administered orally to dogs. Investigation included electromyographic evaluations and biochemical parameter determinations, as well as observable clinical signs. Methods: Six beagle dogs were administered 2,4-dichlorophenoxyacetic acid 200 mg/kg orally. Dogs were monitored for the development of clinical signs and were anesthetized at 24 hours for needle electromyography. Blood was collected pre- and 24-hours postadministration. Plasma was analyzed for total and unbound 2,4-dichlorophenoxyacetic acid by high-performance liquid chromatography with fluorescence detection. Serum was submitted for clinical chemistry parameter analysis. Statistical analyses of the chemistry parameters were performed using paired t-tests. Results: All 6 dogs survived after oral administration of twice the reported LD50. Clinical signs observed were vomiting in 33% and diarrhea in 100% of the dogs. No gait abnormalities were seen in awake dogs. Electromyographic findings revealed predominantly insertional myotonia with 1 dog having spontaneous fibrillations. Decreases from baseline measurements were seen in serum calcium, potassium, and total bilirubin. The mean total and unbound plasma 2,4-dichlorophenoxyacetic acid concentrations were 511 mg/L and 129 mg/L, respectively. Conclusions: This study demonstrates that the beagle dog is less sensitive to the acute effects of 2,4-dichlorophenoxyacetic acid than previously reported. The main clinical effects seen after oral administration of twice the reported LD50 were vomiting and diarrhea. Total and unbound plasma 2,4-dichlorophenoxyacetic acid concentrations may be a useful indicator of toxicity.

Pharmacokinetics of intravenous and oral prethcamide in horses

The respiratory stimulant prethcamide is a mixture of equal parts of crotethamide and cropropamide. A specific and sensitive gas chromatographic method for the determination of crotethamide and cropropamide in horse plasma and urine is described. Both components of prethcamide were extracted from plasma and urine into dichloromethane. The extracts were analyzed by capillary gas chromatography with thermionic detection in the nitrogen-specific detection mode. The lower limits of quantitation were 4.0 ng ml-1 of plasma and 10.0 ng ml-1 of urine. Calibration curves were linear from 2.0-100 ng ml-1 of plasma for both components. Pharmacokinetic parameters for crotethamide and cropropamide after intravenous and oral dosing were estimated by analysis of plasma concentration versus time data. The total plasma clearance of cropropamide was greater than that of crotethamide and both values were greater than 5 ml min-1 kg-1. Renal clearance values of the two drugs were comparable and were much less than estimates of filtration clearance values in horses, indicating extensive re-absorption of both components from the renal tubules. Both compounds were metabolized by N-demethylation of the [(dimethylamino)-carbonyl]-propyl moiety and these metabolites were excreted in urine. The method was demonstrated to be suitable for detecting illicit administration of prethcamide to competition horses.

Zinc effects on nickel dermatitis in the guinea pig

Prevention of NiSO4 induced allergic, contact dermatitis (ACD) using ZnSO4 in drinking water was studied in a guinca pig model Without ZnSO4 intervention, nickel (Ni)‐exposure resulted in significantly higher (p<0.05) stimulation indices (SIs) as compared to non‐exposed controls, using NiSO4 as an allergen in the lymphocyte transformation test (LTT). Oral intake of ZnSO4 at both 250 μg/ml double‐distilled deionized water (DDD) and 500 μg/ml DDD resulted in lower SIs than those of control guinea pigs drinking only DDD: the 250 μg ZnSO4/ml group had significantly lower Sis than (p= 0.025) than controls. There was no significant correlation between intradermal test responses and the SI values of individual guinea pigs exposed to NiSo4 Mean Zinc (Zn) concentrations in skin and in whole blood were not statistically different between the NiSO4 exposed control and Zn supplemented groups, nor between Ni‐sensitive and non‐sensitive animals within groups. The rôle of Zn homeostasis role of the Langerhans cell, effect of Zn supplementation on Ni ACD in other species, and possible blocking effects of other metals should be investigated in future studies.

Postnatal Development of Hepatic Drug-Metabolizing Enzymes in the Gunn Rat

The postnatal development of hepatic drug-metabolizing enzyme activity was compared in icteric homozygous and nonicteric heterozygous Gunn rats. Measurement of enzyme activity was performed by

Factors Affecting Drug Withholding Time Estimates in Horses

Although all the factors discussed in this article may have an effect on drug withholding time estimates, the factors that have the potential for the greatest effect or that have been found to cause positive tests in the past are 1. Dosage: Increasing the drug dosage will require a longer withholding time. 2. Dosing interval: Narrowing the dosing interval will require a longer withholding time. 3. Administration route: In general, oral administration results in lower peak plasma concentrations but may result in longer excretion in the urine and therefore longer withholding time. 4. Drug interaction: The co-administration of drugs may result in interference with the clearance of either drug requiring longer withholding times. It should be noted that environmental chemicals, natural substances in feeds, and other substances have the potential to alter the rate of elimination of a drug. 5. Exercise: Exercise may have a significant effect on the excretion of a drug or its metabolites in the urine. The magnitude of this effect is primarily dependent on the nature of the drug and the mechanisms involved in the renal excretion of the drug. These effects may be important if experimental studies in resting horses are used to estimate withholding times. 6. Analytic method: A change in a screening test for a therapeutic medication by the laboratory may dramatically increase the withholding time for that drug. Veterinarians need to work closely with racing commissions and horse show associations to encourage them to provide advanced notice of such changes and to provide revised withholding time estimates. The attending veterinarian should explain the caveats of withholding time estimates to the trainer or owner to avoid misunderstandings in the event of a positive test. However, the decision to enter the horse in competition after drug treatment is ultimately the responsibility of the trainer and owner.