The Distribution and Excretion of Phenobarbital1

Abstract

The proportional change in the concentration of the undissociated form resulting from change of pH in the physiological range is greater for phenobarbital, with a pK'' of 7.2, than for other familiar barbiturates, which have higher values of pK''. In the concentrations of practical interest, phenobarbital is bound to the extent of about 40% in a 4 g/100 ml solution of serum albumin. The binding is nearly independent of pH. In dogs the plasma phenobarbital concentration falls as the blood pH falls and rises as the blood pH rises. Tissue/plasma concentration ratios vary in a direction opposite to that of the blood pH. Alkalosis, by diminishing the amount of drug in the brain, lightens phenobarbital anesthesia. The renal clearance of pheno-barbital increases with increasing rate of urine, flow. At any given rate of flow, the clearance is much higher when the urine is alkaline than when it is acid. This can be explained on the assumption that the renal tubule is permeable to the undissociated form and impermeable to the ionic form of phenobarbital. Intravenous infusion of a concentrated NaHCO3 solution is suggested for the treatment of phenobarbital poisoning.