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The effect of griseofulvin treatment on signal grass (Brachlaria decumbens) toxicity was studied in 27 male Wiltshire Indigenous Malaysian crossbred sheep. Grazing on signal grass generally decreased the activity of the drug metabolizing enzymes in livers and kidneys. Griseofulvin oral administration of 5 mg/kg body weight for 5 consecutive days every other week for 10 w increased the hepatic concentration of cytochrome P-450 and the activity of phase II drug metabolizing enzymes (UDP-glucuronyltransferase and glutathione-S-transferase) while it decreased the hepatic and increased the renal activity of phase I enzymes aminopyrine-N-demethylase and aniline-4-hydroxylase. Griseofulvin did not protect sheep against B decumbens toxicity as 5/7 animals treated with griseofulvin and grazed on B decumbens showed signs of the plant toxicity.

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The effect of Brachiaria decumbens (signal grass) on drug-metabolizing enzymes was studied in sheep. After 14 d of grazing a pure signal grass pasture, significant declines were observed in hepatic aminopyrine N-demethylase and aniline 4-hydroxylase (phase I biotransformation) and in conjugative enzymes UDP-glucuronyltransferase and glutathione S-transferase. Kidney enzymes were significantly decreased except for UDP-glucuronyltransferase. Enzyme activities were also compared for normal sheep and cattle livers and kidneys. Lower activities were found in cattle, indicating that factors other than biotransformation are responsible for the clincial tolerance of cattle to B. decumbens toxicity.

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1. The effects of various levels of dehydration induced by water deprivation were studied in six Nubian goats on the pharmacokinetics of oxytetracycline after intravenous administration (5 mg/kg). 2. In goats that had lost an average of 7.6% body weight after 2 days of water deprivation, the elimination rate constant of the drug was significantly decreased (P<0.01) and the total body clearance was significantly slower (P<0.001). No statistically significant changes were observed in the pharmacokinetic parameters describing the distribution of the drug at this dehydration level. 3. Water deprivation for 3 or 4 days resulted in a level of dehydration at which the goats lost an average of 10.3% or 12.7% of their body weight, respectively; significant changes were observed in the pharmacokinetic distribution and elimination parameters of oxytetracycline. The volume of distribution at steady state was significantly decreased (P<0.01). Significantly slower total body clearance (P<0.001) and subsequent prolongation of the elimination half-life were found at these dehydration levels. 4. The alterations caused by dehydration on the disposition kinetics of the drug should be considered for better definition of dosage regimens for sick, dehydrated animals.

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Although Brachiaria decumbens was not toxic when fed to cattle, the infusion of rumen liquor from B. decumbens intoxicated sheep into the rumen of cattle produced evidence suggesting hepatic and renal dysfunction. Several biochemical changes were observed including increases in serum aspartate amino transferase, serum creatinine and blood urea nitrogen and a marked reduction in the plasma bromosulphthalein clearance.

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Injectable vitamin A was given to six pregnant beef cows in their last third of pregnancy to study the effect of this vitamin in their calves. Average birth weight and growth rate of calves from the treated cows were higher than that of calves from the nontreated cows. Prepartum vitamin A injections also resulted in a significant increase (P less than 0.05) in the mean corpuscular volume (MCV), total serum protein and globulin fraction of serum protein in calves of treated cows.

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The influence of fever, induced by different agents, on the disposition kinetics of imidocarb was determined in goats. Escherichia coli endotoxin (0.2 microgram/kg), Trypanosoma evansi (10(7) in 1 ml sterile glucose citrate), and Infectious Bovine Rhinotracheitis virus (10(6.5)TCID50) were the agents administered to induce the febrile state. In control and febrile animals the two-compartment model was used to describe the disposition kinetics of the drug. Fever caused significant changes to occur in the apparent volume of distribution and the body (systemic) clearance of imidocarb, but the half-life remained unchanged. The statistical significance of the changes in these pharmacokinetic parameters varied with the etiology of the febrile state. E. coli endotoxin and IBR virus caused corresponding decreases in apparent volume of distribution and clearance of imidocarb, while fever induced with T. evansi caused highly significant increases in both pharmacokinetic parameters. It was concluded that the alterations in the disposition kinetics of imidocarb that occurred in the febrile goats were related not only to the febrile reaction per se but also to the pathophysiology of the disease condition.

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