THE RELATIONSHIP OF THE HUMAN PLASMA PROTEINS IN THE ACTION AND TRANSPORT OF PENICILLIN

¹ Parmly Research Laboratory, Department of Medicine, Northwestern University Medical School, Research Division, Armour and Company and The Miner Laboratories, Chicago, Ill.

1. A series of studies was carried out on the plasma obtained from normal human subjects after the administration of penicillin.

2. Bio-assays for penicillin were performed before and after the fractionation of the plasma into its component protein fractions.

3. It was observed that penicillin could be quantitatively recovered in Fraction VI, which in actuality represents the residue left over after all other fractions have been precipitated. It contains only 2 per cent of the total plasma protein.

4. Dialysis experiments were set up in which identical penicillin concentrations in buffered saline were dialyzed against 3 per cent albumin and buffered saline controls. Bio- and chemical assays for penicillin within attainable blood level concentrations indicated no combination of the penicillin with the protein fraction. Increasing the penicillin concentrations far beyond attainable therapeutic blood levels resulted in binding of about two molecules of penicillin per molecule of albumin. The data obtained indicate that statistical forces predominate.

5. It appears that though a protein-penicillin complex occurs it is of a nature or type which is readily dissociated when the penicillin concentration is low. It therefore seems indicated that transport of penicillin G becomes a function of its solubility in the plasma rather than a function of its protein interaction.