Biopharmaceutical factors influencing LD50. Part II: Particle size

The effect of particle size on the time elapsing between administration and loss of righting reflex and % of deaths by determining the LD50 has been studied in mice. The drug used was pentobarbituric acid. In one preparation the particle size was less than 44 mum and in the other preparation it was greater than 297 mum and less than 420 mum. For both preparations a 1% sodium carboxymethylcellulose solution was used as suspending medium. It was found that both the curve for loss of righting reflex and the log dose-response curve, and hence the LD50, were significantly shifted to the right. There is a reflex LRR between the suspended pentobarbituric acid and the equivalent amount of sodium pentobarbital, both in 1% sodium carboxymethylcellulose solution. In reporting LD50 data it is essential not only to state the exact composition of the vehicle (viscosity factor) but also to state the exact particle size or particle size range, because by using increasing particle size the LD50 decreases.