Study of the metabolism of barbiturates in the horse

Abstract

(a) The amounts of pentobarbitone and phenobarbitone able to be given to ponies, without risking respiratory arrest, was low in comparison with other species.

(b) Ultra-violet spectrophotometry has been shown to be of limited value for general use in quantitative and qualitative analysis of horse blood and saliva samples for pentobarbitone and phenobarbitone.

(c) Pentobarbitone had a mean blood clearance rate of 46%/hour (S.D. 8%/hour, n = 6) when given by intravenous injection and this was paralleled in the saliva.

(d) The blood clearance rate of phenobarbitone was found to be non—logarithmic over the time 0 to 6.5 hours after oral administration and this was paralleled in the saliva.

(e) The degree of plasma protein binding was shown to be 43% and 15% for pentobarbitone and phenobarbitone respectively. Pentobarbitone was shown to be not protein bound in saliva, but phenobarbitone was found to be bound to a small extent i.e. 7%.

(f) No effect was observed on the rate of normal saliva flow following barbiturate administration. The concentration of the two barbiturates in the saliva was found to be independant of the saliva flow rates, although phenobarbitone concentrations were subject to considerable fluctuations.

(g) The concentration of barbiturate in the saliva was directly dependant on the concentration of non-protein bound barbiturate in the blood.

(h) Phenobarbitone, the presence of which was not easily demonstrated, was excreted in horse urine to the extent of about 10% in the 72 hours following oral dosage of the drug.

(i) p-hydroxyphenobarbitone was the only metabolite of phenobarbitone detected in horse urine and was conjugated with glucuronic acid.

(j) Pentobarbitone was metabolised in the horse to the 5-ethyl-5-(3-hydroxy-I-methylbuty1) barbituric acids and to 5-ethyl-5~( 3-methyl-I-carboxypropyl) barbituric acid. The alcohol metabolites, of which no evidence of glucuronic acid conjugation was found, were completely excreted in urine over a period of 21 hours after oral administration and accounted for 33% of the administered drug.