THE RELATION OF PROTEIN BINDING TO THE PHARMACOLOGY AND ANTIBACTERIAL ACTIVITY OF PENICILLINS

It is well recognized that many substances which inhibit bacterial growth in vitro may lose a part or all of this antibacterial activity in the presence of human serum. This phenomenon is attributed in part to the fact that the antibacterial agents are adsorbed or otherwise bound to some constituent of serum. The role of the serum proteins in this process has recently been reviewed by Davis (1946). It has been demonstrated by Davis (1942, 1943) and by Gilligan (1943) that the individual sulfonamides are bound to serum albumin to a varying degree, and there is suggestive evidence that the portion of the drug which is bound is inactive against bacteria. Chow and McKee (1945) have shown by dialysis experiments that crystalline penicillin (G) is bound to serum albumin. Similar results were reported from this laboratory in experiments, in which whole serum and crude penicillinwere used (McDermott and Nelson, 1945). In the latter experiments, the anti-bacterial activity of the penicillin-serum complex was not studied. Chow and McKee believed, however, that, although the penicillin was bound to a significan