Enzymatic activation of Clostridium perfringens epsilon prototoxin removed a small basic part of the molecule, causing a slight change in molecular weight (32,700 to 31,200) and a large change in isoelectric point (from pH 8.02 into fractions of 5.36 and 5.74).

The pharmacokinetics and bioavailability of theophylline in horses were investigated following both intravenous and intragastric administration of aminophylline solutions at doses corresponding to 15 and 10 mg/kg theophylline base. A rapid distributive phase with a half-life of approximately 15-30 min was followed by a slower elimination half-life averaging 15-17 h. The apparent volume of distribution averaged 850-900 ml/kg. Theophylline, administered as aminophylline solution, was both rapidly and completely absorbed from the equine digestive tract. Based on the bioavailability and disposition kinetics of theophylline, an intragastric dosage regimen for aminophylline consisting of the administration of 5 mg/kg at 12 h intervals would be expected to maintain plasma theophylline concentrations within the therapeutic range.

INTRODUCTIONKrimpsiekte, a chronic form of cardiac glycoside poisoning, manifests as a paretic syndrome and occurs predominantly in small stock 5,6 . The disease develops following ingestion of certain members of the Crassulaceae (Cotyledon, Tylecodon and Kalanchoe species). Krimpsiekte is generally believed to be caused by cumulative bufadienolides, with unique neurotoxic properties, encountered in these genera 5,7 . Naudé and Schultz 8 coined the term 'cumulative bufadienolides' following the successful demonstration of a cumulative effect with cotyledoside isolated from Tylecodon wallichii. These authors determined a subcutaneous LD50 of 0.116 mg/kg cotyledoside in guinea pigs and then injected others subcutaneously with 25 % and 50 % of the subcutaneous LD50 per day until they died. No clinical signs appeared before the LD50 was reached and marked nervous signs occurred when 5 × 25 % or 3 × 50 % the LD50 were administered 8 .Repeated intravenous cotyledoside administration at 0.01-0.015 mg/kg body mass to sheep induced krimpsiekte,

Investigaltions to determine the effect of sample storage on the concentration of copper in liver tissue and on the activity of erythrocyte superoxide dismutase were undertaken in preparation for a study of blesbok (<em>Damaliscus pygargus phillipsi</em>) that were suspected to be suffering from copper deficiency. Two liver samples were collected from each of 20 culled blesbok in a manner that simulated the collection of biopsies from the live animal. These samples were stored either in 10 % formalin or frozen at -20 °C until analysed 4 1/2 months later. The effect of different methods of sample storage on superoxide dismutase activity was determined. Erythrocytes collected from 3 Jersey cows and 5 culled blesbok were washed and divided into 0.5m portions, stored at room temperature (~20 °C), in a refrigerator (4 °C), frozen at -20 °C in a freezer, and in liquid nitrogen (-200 °C). An analysis of superoxide dismutase activity was undertaken using a commercial assay kit at intervals of 2-4 days until the levels of activity had fallen significantly. The copper concentration in formalin-preserved liver samples was significantly lower than that measured in frozen liver tissue apparently as a result of leaching. The activity of superoxide dismutase in cattle blood was unchanged for 4 days at room temperature but fell appreciably after 2 days at 4 °C and -20 °C. Enzyme activity remained unchanged for 200 days in erythrocytes stored in liquid nitrogen. Superoxide dismutase activity levels in healthy blesbok were considerably lower than those measured in Jersey cows and remained unaffected for up to 6 days in samples stored at 4 °C and 20 °C. The level of activity fell significantly thereafter. Samples stored in liquid nitrogen were unchanged after 40 days

The plasma and salivary disposition of closantel and rafoxanide were examined following intravenous administration in adult sheep. Two studies were conducted with rafoxanide at 7.5 mg/kg and 1 with closantel using 2 doses (5 and 15 mg/kg). The pharmacokinetic profile of both drugs in plasma were best described by a 2-compartmental model with 1st-order rate constants. Plasma disposition of closantel and rafoxanide were characterised by a rapid distribution (t1/2(a) of &lt;30 min), long elimination half-life (t1/2(b) of 17.0 + 4.0 days for closantel and 7.2 + 0.6 days for rafoxanide), small apparent volume of distribution (Vss of &lt;0.15 ℓ/kg) and a slow rate of total body clearance (Cl of &lt;0.01mℓ/min/kg). The area under the drug plasma concentration curve (AUC) of closantel at 5 mg/kg was nearly twice as large as that of rafoxanide at 7.5 mg/kg resulting from the slower t1/2(b) observed with closantel compared to rafoxanide. Large individual differences were observed in the rate measurements of distribution (k12, k21 and t1/2(a)), whereas the parameters of elimination (k10, t1/2(b) and Cl), were more consistent between animals. A dose proportional increase in AUC was observed for closantel administered at 5 and 15 mg/kg. A low, constant salivary concentration of closantel (mean of 0.04+0.05 mg/mℓ) and rafoxanide (mean of 0.07+0.04 mg/mℓ) was observed during the 24-h examination period after dosing