STUDIES ON BARBITURATES XII. FACTORS GOVERNING THE DISTRIBUTION OF BARBITURATES

¹ From the Department of Pharmacology and Materia Medica, Georgetown University, School of Medicine, Washington, D. C.

The rate of disappearance of barbital from the blood varies inversely with the dose, and conversely, the rate at which organs take up barbital is relatively faster after small than after large doses.

Barbital disappears from the mammalian blood faster than from the blood of fowls.

The rapidity of taking up of barbital from the blood varies with different structures, and possibly depends on the circulation through the organ and other physical factors.

Barbiturates can be detected in the blood as long as they are present in the tissues.

No organ or tissue has any specific affinity for barbiturates. However, after barbital administration the brain contains less, and after pentobarbital-sodium (nembutal) administration it contains more barbiturate than other organs.

The barbital binding capacity of the brain may be enhanced by the injection of this drug dissolved in 50 per cent methanol into the carotid artery.

The administration of pentobarbital-sodium in aqueous or alcoholic solutions by any route results in higher concentrations of this drug in the brain than in other organs.

It is impossible to saturate organs by direct injection of concentrated solutions of barbiturates into their main artery, because the rest of the body acts as a "buffer" and the drugs are quickly distributed among the different tissues. The rate of this desaturation of the directly injected organs may be measured at various time intervals by a determination of the barbiturate content of the venous blood returning from the injected organ.

Saturation of organs with barbiturates can only be accomplished by the administration of massive doses to an animal.