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Local anesthesia and tissue inflammation associated with lidocaine infiltration and lidocaine/prilocaine topical anesthetic cream for episioplasty in mares were compared. Twenty-two mares were randomly assigned to lidocaine or lidocaine/prilocaine topical anesthetic cream treatment groups. Perineum and vulva were cleaned, 8-12 g (approximately 1 g/cm per side of vulva) of topical anesthetic cream was applied, and the area was covered by plastic wrap 30 min prior to beginning procedure. Alternately, lidocaine was injected (1 mL) every centimeter just prior to the procedure. Episioplasty was conducted using standard methods, but employing simple interrupted sutures. Horses were not sedated and use of a twitch was recorded. Four millimeter punch biopsies were harvested 1, 3, and 10 days following episioplasty and scored for degree of inflammation by a blinded pathologist. Clinical inflammation scores were assigned when biopsies were obtained. Seven of 11 horses receiving lidocaine infiltration required twitching, but none of the horses that received the anesthetic cream required twitching. Six of 11 and seven of 11 of the lidocaine and anesthetic cream groups, respectively, required twitching for episioplasty. Except for the clinical scores on day 3, no statistical differences for clinical and histopathologic scores between samples from the two treatment groups for a given day were identified. Use of lidocaine/prilocaine topical anesthetic cream was as effective as lidocaine infiltration in providing local anesthesia when performing episioplasty in mares. Its use decreased the need for twitching horses as well as the risk of deformation of the labia caused by lidocaine infiltration.

Objective: To determine the pharmacokinetics of acetazolamide administered IV and orally to horses., Animals: 6 clinically normal adult horses., Procedure: Horses received 2 doses of acetazolamide (4 mg/kg of body weight, IV; 8 mg/kg, PO), and blood samples were collected at regular intervals before and after administration. Samples were assayed for acetazolamide concentration by high-performance liquid chromatography, and concentration-time data were analyzed., Results: After IV administration of acetazolamide, data analysis revealed a median mean residence time of 1.71 +/- 0.90 hours and median total body clearance of 263 +/- 38 ml/kg/h. Median steady-state volume of distribution was 433 +/- 218 ml/kg. After oral administration, mean peak plasma concentration was 1.90 +/- 1.09 microg/ml. Mean time to peak plasma concentration was 1.61 +/- 1.24 hours. Median oral bioavailability was 25 +/- 6%., Conclusions and Clinical Relevance: Oral pharmacokinetic disposition of acetazolamide in horses was characterized by rapid absorption, low bioavailability, and slower elimination than observed initially after IV administration. Pharmacokinetic data generated by this study should facilitate estimation of appropriate dosages for acetazolamide use in horses with hyperkalemic periodic paralysis.

Ten healthy horses were injected intravenously with 99mTc-MAG3 and the disappearance of radioactivity from the blood was measured. The total body clearance (Cl(B)) and elimination half-life (t1/2(beta)) were 7.9 +/- 1.5 ml/kg/minute and 32.8 +/- 4.1 minutes, respectively. The disappearance of 99mTc-MAG3 from the blood of 2 horses with compromised renal function was also measured. The data suggest that 99mTc-MAG3 is a useful and clinically applicable radiopharmaceutical for measurement of effective renal blood flow in the horse.

Phenylbutazone given during the perisurgical period has been reported to increase the intensity and duration of thiamylal anaesthesia in horses. A possible mechanism of competitive plasma protein binding has been suggested. The purpose of the present study was to experimentally reproduce the phenomenon of increased intensity and/or duration of thiamylal anaesthesia and to determine if there is competitive displacement of plasma protein bound thiamylal by phenylbutazone. Six ponies each received one of three treatments, 11 mg/kg intravenous (i.v.) thiamylal; 8.8 mg/kg i.v. phenylbutazone; and 11 mg/kg i.v. thiamylal with 8.8 mg/kg i.v. phenylbutazone given 9 min later. Thirteen blood samples were collected from 0 time through 600 min following drug administration and plasma drug concentrations quantified by high performance liquid chromatography. The pharmacokinetics of thiamylal and phenylbutazone were best described by three- and two-compartment models, respectively. There were no significant differences in pharmacokinetic parameters for thiamylal in the presence of phenylbutazone. However, there were differences in phenylbutazone pharmacokinetics when preceded by thiamylal administration. Unbound phenylbutazone concentrations were increased at 171, 231 and 351 min when given with thiamylal, accompanied by decreases in per cent bound phenylbutazone (P < 0.05). There were also significant (P < 0.05) changes in per cent plasma protein binding of thiamylal and phenylbutazone between 120 and 360 min, when in combination. No changes in intensity or duration of anaesthesia were observed.

Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered IV and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The IV and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after IV administration was 1,521 ml/kg and the median elimination half-time was 12.06 hours. Mean plasma concentration after oral administration fluctuated between a maximal concentration of 0.18 microgram/ml and 0.09 microgram/ml (24 hours after dosing). Bioavailability after oral administration was 56%.

Pharmacokinetics, CSF penetration, and hematologic effects of oral administration of pyrimethamine were studied after multiple dosing. Pyrimethamine (1 mg/kg of body weight) was administered orally once a day for 10 days to 5 adult horses, and blood samples were collected frequently after the first, fifth, and tenth doses. The CSF samples were obtained by cisternal puncture 4 to 6 hours after administration of the first, third, seventh, and tenth doses. Pyrimethamine concentration in plasma and CSF was quantified by gas chromatography, and plasma concentration-time data were analyzed, using a pharmacokinetic computer program. Repeated daily dosing resulted in accumulation of pyrimethamine in plasma, with steady state being achieved within 5 days, when the mean peak plasma concentration was more than twice that measured after the first dose. Pyrimethamine concentration in CSF was 25 to 50% of corresponding plasma concentration and did not appear to accumulate with successive administration of doses. Blood samples collected during and after the dosing regimen were submitted for hematologic analysis; neutrophil numbers decreased slightly, but remained within normal range for adult horses.

Several studies conducted during the past few years have shown that the pharmacokinetics of a variety of drugs may be altered following viral infection or vaccination. The elimination of drugs which are extensively metabolized, such as theophylline, may be prolonged, especially following exposure to RNA viruses such as Type A influenza or similar orthomyxoviruses. The purpose of this study was to determine whether vaccination of horses with equine influenza virus affected pharmacokinetic parameters describing the distribution and elimination of intravenously administered theophylline. Three thoroughbred horses and three ponies were vaccinated with a trivalent vaccine containing inactivated strains of A/Equi 1 (Prague), A/Equi 2 (Miami) and A/Equi 2 (Kentucky 81). Antibody titre, serum interferon concentrations, and the pharmacokinetic parameters t1/2 beta, Vc, Vd(ss), Vd(area) and ClB were measured at various intervals after vaccination. Antibody titre increased substantially in only two animals, while plasma interferon was detectable in low concentrations in four subjects. There was no significant change in any parameter describing the pharmacokinetics of theophylline when measured 2, 6, or 12 days after vaccination. It is suggested that the failure of vaccination to substantially increase plasma interferon concentrations, and thereby alter theophylline elimination, was related to the use of an inactivated viral vaccine, the only type available for vaccination of horses against infection with equine influenza. Regular use of such vaccines, as is required by most Racing Authorities, is therefore unlikely to affect drug withdrawal times.

The pharmacokinetics of cephapirin sodium and its distribution into a tissue chamber implanted subcutaneously in the neck of mature horses are described. Cephapirin was administered as an intravenous bolus dose of 20 mg/kg. The serum concentration vs time curve was best described by a two-compartment open model. Cephapirin disappeared from serum rapidly (t1/2 beta = 18.8 min), and had only a modest volume of distribution (Vd(area) approximately equal to 346 mg/kg, Vd(ss) approximately equal to 204 ml/kg). Total clearance was also rapid (approximately equal to 13 ml/min.kg). Concentrations of the antibiotic in tissue chamber fluid, however, were quite constant from 30 min to 3 h post-injection, and did not decay in parallel with either the concentration of the drug in serum or the estimated concentration of drug in the peripheral compartment. The ratio of area under the curve (AUC0-3 h) for serum: chamber fluid was 13.8 : 1, while that for peripheral compartment : chamber fluid was 11 : 1. The slow rate of cephapirin transport into, and out of, the chamber may be related to its hydrophilic nature. The lack of parallelism between the chamber fluid decay curve and that of serum is characteristic of drugs with a very short half-life.