BLOOD LEVELS OF SULFADIAZINE, SULFAMERAZINE AND SULFAMETHAZINE IN RELATION TO BINDING IN THE PLASMA

¹ From the New York Hospital and the Department of Medicine, Cornell University Medical College, New York, N. Y.

1. In vitro dialysis studies show sulfamerazine and sulfamethazine to be bound in the plasma to a much greater extent than is sulfadiazine. Similarly, their acetyl derivatives are more highly bound in the plasma than is acetylsulfadiazine.

2. At a drug concentration of 10 mgm. per 100 cc. in plasma of pH 7.4 and containing 7.0 gm. per 100 cc. of protein, only 16 per cent of the plasma sulfamerazine and sulfamethazine are freely diffusible as compared with 44 per cent for sulfadiazine.

3. Estimations of the extent of binding in vivo, made from available data on absorption, excretion and blood levels in man after single doses of these three drugs, afford evidence that the binding of the drugs in the plasma in vivo is essentially the same as was found in the in vitro studies.

4. It is calculated that a blood level of 20 mgm. per 100 cc. of sulfamerazine or of sulfamethazine provides a concentration of dialyzable drug in the plasma and tissues approximately the same as is provided by a blood level of only one-half this amount of sulfadiazine.

5. The results of in vitro studies of red cell:plasma ratios of all these drugs were very variable. The red cell:plasma ratios of the acetyl derivatives of the drugs were generally lower than those of the parent drugs.

6. The relative extent of binding of these drugs in the plasma is discussed with respect to the interpretation of absorption rates from the rate of increase of the blood concentration of the drugs and with respect to its possible bearing on the relative therapeutic effectiveness of a given blood level of the different drugs.