Studies on serum protein binding and its influence on active blood level of chemotherapeutic agents.

It is well recognized that many chemotherapeutic agents are inactivated in vivo and may lose a part or all of their antibacterial activities. Davis' 2 has described that this phenomenon is attributed in part to the serum protein binding of the antibacterial agents. After this report, the extensive studies on protein binding of sulfonamids,3 penicillins; 9 tetracyclines10-'2 and other chemothera peutic drugsl3-1s have been carried out. Nevertheless these data are still incom plete in certain respects. For example, the binding rates of certain drugs are different in these reports, because the methods of assay or sera used are different. Furthermore, as Bond3 has pointed out, even when the same method and the same serum were used, there were individual variations in binding rate of the drug to serum protein. But there was a methodological problem in the report of Bond. So there is no report that may clarify the individual variations in the binding rate of the drug to serum protein. On the other hand, it is also recognized that the acetylation is another factor of inactivation of certain drugs, and this process of inactivation was extensively studied on INH. Those studies indicated that the individual variations of bacteriologically active blood levels of INH were due to the differences of acetylation rates. Consequently, the protein binding and acetylation of certain drugs may be the most important metabolic process of drug inactivation in vivo. But, in the above mentioned literatures, the relation between these two factors was never been discussed. The present author carried out the following experiments with