The Relation of Protein Binding to the Pharmacology and Antibacterial Activity of Penicillins X, G, Dihydro F, and K

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Abstract
When the efficiency of various penicillins in 30% serum and 2% blood broth was compared, it was found that penicillins X, G, dihydro F were 36, 41, and 43% efficient in serum, respectively; penicillin K was only 7% as efficient in serum. The growth of the test organism, Streptococcus hemolyticus, was not altered by the additions of 10-30% serum to the broth medium. Penicillins G and K (10 U./ml.) incubated with whole serum were almost completely inactivated in 24 hrs.; however, in expts. more comparable to those encountered in routine bio-assays of serum samples, e.g., 0.2-0.5 U./ml. in 10-30% serum, no inactivation occurred in 12 hrs. The degree of binding of these penicillins to proteins was detd. by dialysis. It was found that penicillins G, X, dihydro F and K were bound to some constituent of serum (mainly albumin plus some other factor(s)) 47, 58, 63, and 91%, respectively. The degrees of reduction in antibacterial activity were roughly proportional to the degree of binding. The relation of these findings to bio-assays of serum samples, and pharmacologic studies is discussed. Concerning possible application to therapy, the authors point out that there is an inverse relation between the in vitro binding of the individual penicillins, and the reported effectiveness of these penicillins in the treatment of exptl. in-fections.