Pharmacokinetics, penetration into cerebrospinal fluid, and hematologic effects after multiple oral administrations of pyrimethamine to horses.

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.     

The outbreak of equine influenza in England: January 1976.

Equine influenza type 2 infections occurred in the Newmarket areas in January 1976. The disease did not spread to any extent and while this may have been due to recent vaccination it was found that not all vaccinated horses were fully protected. The virus involved showed some antigenic drift from the prototype strain A/equine/Miami/1/63 (Heq 2 Neq 2).     

Experimental chloramphenicol intoxication in neonatal calves: intravenous administration

Chloramphenicol was administered intravenously for eight to 17 days to five newborn calves at a daily dosage of 100 mg kg-1. Haemodynamic, haematological, blood chemistry, serum enzyme, urinalysis and clinical responses were evaluated. High levels of serum chloramphenicol were observed throughout the study although a marked increase in elimination rate was seen with increasing age. The most severe adverse effects were severe hypotension following rapid intravenous administration and severe gastrointestinal dysfunction with diarrhoea accompanying prolonged high dosage. There appeared to have been a haematological effect in one calf, but it was of minor significance compared with the other effects.     

In vitro assessment of the efficacy of erythromycin in combination with oxytetracycline or spectinomycin against Pasteurella haemolytica

The effects of combining erythromycin (Ery) with oxytetracycline (Oxy) or spectinomycin (Sp) on Pasteurella haemolytica were evaluated in vitro using the chessboard (checkerboard) technique. These combinations were selected because all are drugs widely used in bovine respiratory disease treatment, and they represent possible sequential or complementary mechanisms of action. Using the recommended breakpoints of greater than 4 micrograms/ml for Ery, 16 micrograms/ml for Oxy, and 32 micrograms/ml for Sp, of the 33 P. haemolytica isolates, 32 were resistant to Oxy, 27 to Sp, and 14 to Ery. Based on the fractional inhibitory concentration index, Ery and Oxy in combination were synergistic or additive against 32 of 33 isolates. The combination of Ery and Sp was synergistic or additive against 27 of 33 isolates. No instances of antagonism were seen. When the effects were considered within the context of therapeutically achievable serum/tissue concentrations, the effects of Ery and Oxy in combination were only marginal. Thus, against P. haemolytica isolates, Ery and Sp appeared to represent an effective antimicrobial combination, whereas Ery and Oxy were only of marginal efficacy as a combination.     

The prophylactic effect of corn supplementation on experimental nitrate intoxication in cattle

Sodium nitrate was administered through rumen cannulae to produce NO-3 intoxication in four cows (382 to 445 kg body wt) fed prairie grass hay and a protein-mineral supplement. The cows were fed 0, 1.6 or 3.2 kg of dry rolled corn daily for 10 d prior to sodium nitrate administration. Sodium nitrate administration was followed by a marked increase in intraruminal NO-2 and NH3 and blood NO-2 and methemoglobin. Six of eight cows fed 0 and 1.6 kg of corn were given methylene blue to treat severe methemoglobinemia, while none of the cows fed 3.2 kg corn required such therapy. Feeding of 3.2 kg of corn protected against nitrate poisoning by reducing intraruminal nitrite and blood methemoglobin (P less than .05).     

Hypotension produced by rapid intravenous administration of chloramphenicol in anaesthetised dogs

Rapid intravenous administration (60 mg s-1) of chloramphenicol (50 mg kg-1) in a 40 per cent w/v polyethylene glycol (400 to 600), 30 per cent ethyl alcohol, 2 per cent benzyl alcohol and 28 per cent distilled water vehicle produced a transient but significant decrease in systemic arterial blood pressure and heart rate with no effect on central venous pressure in sodium pentobarbital anaesthetised dogs. The vehicle alone had no significant effect on any of the parameters studied. Various approaches including the use of anticholinergic, antihistaminergic, antiadrenergic and ganglion blocking drugs failed to attenuate chloramphenicol induced hypotension and bradycardia. However, the hypertensive response to bilateral carotid arterial occlusion was significantly attenuated by rapid intravenous administration of chloramphenicol. The results clearly indicate that chloramphenicol itself, but not its vehicle, is responsible for the severe hypotension and bradycardia. These results also suggest that chloramphenicol-induced hypotension and bradycardia might be mediated peripherally via vasodilation due to its direct effect on vascular smooth muscle and centrally via interruption of the baroreceptor reflex pathway.     

Effects of allopurinol in experimental endotoxin shock in horses

The effect of allopurinol pretreatment 12 hours before an intraperitoneal challenge with a sublethal dose of Escherichia coli endotoxin (50 micrograms kg-1) was evaluated in 18 horses. The horses were divided among three equal groups: 1-endotoxin alone; 2-5 mg allopurinol kg-1 bodyweight plus endotoxin; and 3-50 mg allopurinol kg-1 bodyweight plus endotoxin. A variety of evaluation parameters were used. No differences among the groups were noted in rectal temperature, heart rate, respiration rate, haematological values, blood PaO2, blood PaCO2, blood pH or blood bicarbonate. Significant (P less than 0.05) differences between the groups were noted as regards the changes in capillary refill time, base excess, blood glucose, blood lactate, blood beta-glucuronidase and recumbency time. The protection afforded by 5 mg allopurinol kg-1 appeared to be superior to that with 50 mg allopurinol kg-1.