THE BINDING OF SULFONAMIDE DRUGS BY PLASMA PROTEINS. A FACTOR IN DETERMINING THE DISTRIBUTION OF DRUGS IN THE BODY

Abstract

It is proposed that the distribution of drugs in the body fluids, often interpreted in terms of diffusibility or permeability, should be analyzed in terms of thermodynamic activity and binding to protein. Equilibria of sulfonamide drugs, dialyzed between plasma or plasma protein fractions and buffer, show considerable binding of drug to albumin, the extent of which accounts for the distribution of the drugs in the body fluids and the increased solubility in plasma. The order of increasing binding tendency is sulfanilamide, sulfapyridine, sulfadiazine, sulfathiazole. The binding increases with increasing alkalinity over the pH range 6.0 to 8.5, suggesting that anionic dissociation is a factor in the binding. It is probable that only the unbound drug is bacteriostatically active. The effective level of any of the sulfonamides in the cerebrospinal fluid would then be as great as that in the blood stream, suggesting that the ratio of the concs. in spinal fluid and blood should not be used as a guide to the choice of a drug in the treatment of meningitis.