Terbutaline pharmacokinetics in cows: preliminary data.

The objective of this study was to determine the serum pharmacokinetics of terbutaline in healthy cows. In the initial experiment, terbutaline was administered once as an intravenous (i.v.) bolus to 6 near-term pregnant beef cows within 24 h after parturition at a low but therapeutically relevant dose, 5 microg/kg. A 2nd experiment was conducted in the same cows with a higher dose, 0.5 mg/kg, but an otherwise similar experimental design. The serum concentration of terbutaline was determined by means of high-performance liquid chromatography with fluorescence detection in both experiments. After i.v. administration of 0.5 mg/kg, the mean peak serum concentration, residence time, and half-life were 708.22 (standard deviation 509.6) ng/mL, 6.75 (3.6) min, and 6.93 (2.4) min, respectively. The results indicate that terbutaline is rapidly eliminated from the bloodstream after i.v. administration in cattle, falling below the assay's limit of detection 30 min after administration.

Pharmacokinetics of acyclovir after single intravenous and oral administration to adult horses.

The purpose of the study reported here was to describe the bioavailability and pharmacokinetics of acyclovir after intravenous and oral administration to horses. Six healthy adult horses were used in a randomized cross-over study with a 3 x 3 Latin square design. Three treatments were administered to each horse: 10 mg of injectable acyclovir/kg of body weight in 1 L of normal saline delivered as an infusion over 15 minutes; 10 mg of acyclovir/kg in tablets by nasogastric intubation; and 20 mg of acyclovir/kg in tablets by nasogastric intubation. A 2-week washout period was provided between each treatment. Serum samples were obtained for acyclovir assay using reversed-phase, high-performance liquid chromatography with fluorescence detection. Deproteinated serum was injected onto a C18 column, and elution occurred under isocratic conditions. The limit of quantification was 0.04 microg/mL. The assay exhibited suitable accuracy, precision, and recovery. The IV data were analyzed by a 3-compartment model, and oral data were analyzed noncompartmentally. Intragastric acyclovir administration at either dose was associated with high variability in serum acyclovir-time profiles, low Cmax, and poor bioavailability. The dosage of 20 mg/kg was associated with mean (+/- SD) Cmax of 0.19 +/- 0.10 microg/mL, and bioavailability was 2.8%. Inhibition of equine herpesvirus has been reported to require significantly higher acyclovir concentrations than those obtained here. The results of this study do not support a therapeutic benefit for the oral administration of acyclovir up to doses of 20 mg/kg.

Antimicrobial resistance.

Development of antimicrobial resistance is an inevitable consequence of exposure of microorganisms to antimicrobial agents. Although emergence of resistance cannot be prevented, it can be retarded by minimizing use of antimicrobial agents and avoiding selection of relatively resistant pathogenic and nonpathogenic strains caused by exposure to tissue concentrations that confer a competitive advantage. Most attention in veterinary medicine has focused on the emergence of resistance in food-borne pathogens, with relatively little attention being devoted to small companion animals, despite the frequent use of antimicrobial agents in these animals, evidence that resistance is emerging, and potential for transfer of resistance between companion animals and people. To retard further emergence of resistance in small companion animals, it is imperative that surveillance programs be instituted to monitor development of resistance.

Use of force plate analysis to compare the analgesic effects of intravenous administration of phenylbutazone and flunixin meglumine in horses with navicular syndrome.

OBJECTIVE: To use force plate analysis to evaluate the analgesic efficacies of flunixin meglumine and phenylbutazone administered i.v. at typical clinical doses in horses with navicular syndrome. ANIMALS: 12 horses with navicular syndrome that were otherwise clinically normal. PROCEDURE: Horses received flunixin (1.1 mg/kg), phenylbutazone (4.4 mg/kg), or physiologic saline (0.9% NaCI; 1 mL/45 kg) solution administered IV once daily for 4 days with a 14-day washout period between treatments (3 treatments/horse). Before beginning treatment (baseline) and 6, 12, 24, and 30 hours after the fourth dose of each treatment, horses were evaluated by use of the American Association of Equine Practitioners lameness scoring system (half scores permitted) and peak vertical force of the forelimbs was measured via a force plate. RESULTS: At 6, 12, and 24 hours after the fourth treatment, subjective lameness evaluations and force plate data indicated significant improvement in lameness from baseline values in horses treated with flunixin or phenylbutazone, compared with control horses; at those time points, the assessed variables in flunixin- or phenylbutazone-treated horses were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with navicular syndrome treated once daily for 4 days, typical clinical doses of flunixin and phenylbutazone resulted in similar significant improvement in lameness at 6, 12, and 24 hours after the final dose, compared with findings in horses treated with saline solution. The effect of flunixin or phenylbutazone was maintained for at least 24 hours. Flunixin meglumine and phenylbutazone appear to have similar analgesic effects in horses with navicular syndrome.

The role of the clinical pharmacologist in animal health.

Like most scientific disciplines, pharmacology is replete with subspecialties. Certainly most scientists recognize the value of animal studies in drug development for human pharmaceuticals. However, animals as the target species also represent a major focus of investigation. According to recent estimates, in the United States for the year 2000, 98.1 million cattle, 59.8 million pigs, and 1.5 billion chickens existed. Added to that estimate were companion animals, including 4 million horses, 59 million cats, and 52.9 million dogs. The estimate does not include the so-called "minor" species, such as 7 million sheep and 320,000 acres of freshwater fish production. In most respects, the medical needs of these animals are addressed in a manner parallel to that of human medicine. One such parallel, with certain distinct differences from its human counterpart, is veterinary clinical pharmacology.

Ocular penetration of oral doxycycline in the horse.

OBJECTIVE: To investigate intraocular penetration of orally administered doxycycline in the normal equine eye and to compare intraocular and serum doxycycline concentrations. Procedures Six mares were administered doxycycline at 10 mg/kg every 12 h by nasogastric tube for 5 days. Blood, aqueous, and vitreous samples were collected on days 1 and 5. All samples were assayed for doxycycline concentrations. Aqueous and vitreous samples were also assayed for protein quantitation. RESULTS: Doxycycline was rapidly absorbed after the first dose (T(max) value of 1.42 +/- 1.28 h); and elimination of doxycycline occurred slowly (median t(1/2) = 10.88 h). Doxycycline could not be detected in the aqueous on days 1 and 5, nor could it be detected in the vitreous on day 1. On day 5, the mean vitreous doxycycline concentration was 0.17 +/- 0.04 microg/mL at 2 h after drug administration. CONCLUSIONS: Repeated oral administration of doxycycline in the horse resulted in steady state serum concentrations of < 1 microg/mL; however, it did not result in appreciable concentrations of drug in the aqueous and vitreous in normal eyes.