EFFECT OF TEMPERATURE ON TOXICITY AND DISTRIBUTION OF PENTOBARBITAL AND BARBITAL IN RATS AND DOGS

¹ Research Department, Recordati S.p.A., Milano, Italy

The acute toxicity and the death times of pentobarbital and barbital in rats kept at room temperatures of 30°C and 15°C were determined. The blood, liver and brain concentrations of pentobarbital after a single intravenous injection were also studied in rats at these two temperatures. In dogs the blood levels of the two barbiturates after a single intravenous injection were studied at these temperatures. The effect of temperature on the distribution between oil and water and on plasma-proteins binding was also investigated.

It was demonstrated that exposure to a cold environment increased the toxicity of both barbiturates. The animals, however, died more slowly at the lower temperature, especially after pentobarbital poisoning.

At a low room temperature the diffusion from the blood to the tissues and the metabolism of pentobarbital were decelerated and the volume of distribution of this drug decreased quite considerably. Further, exposure to the cold environment reduced the liver-blood and brain-blood repartition coefficients of pentobarbital. None of these changes seems to be in direct correlation with body temperature.

It was not possible to detect any physicochemical properties of pentobarbital so affected by temperature as to explain the phenomena observed.

The rate of diffusion from the blood to the tissues and the apparent volume of distribution of barbital are not affected by room temperature. The effect of room temperature on the rate of elimination of barbital is small and not statistically significant.