Serum Binding,Distribution and Excretion of Four Penicillin Analogues Following Intravenous Injection in Man. ∗

Summary

The in vitro binding to human serum proteins, and the half-life in serum, relative volume distribution and urinary recovery of 4 penicillin analogues, G, V, phenethicillin, and mercaptomethyl penicillin following single intravenous injections in normal male subjects were investigated to aid interpretation of oral absorption studies. Penicillin G was found to be significantly less bound than the others (48.7% compared to 74.4 − 78.8%). Significant differences in relative distribution volumes of the 4 analogues could not be demonstrated due in large part to considerable subject and laboratory variation. The shortest half-life in serum was obtained with penicillin V (0.52 hour), the longest with penicillin G and phenethicillin (0.75-0.78 hour), while phenylmercaptomethyl penicillin was intermediate (0.64 hour). The 24-hour urinary recoveries were penicillin G 46%, V 57%, phenethicillin 60%, and phenylmercaptomethyl penicillin 21%. It is concluded from comparison of these results with those of others that differences noted in protein binding may be outweighted by other considerations such as cost, optimum therapeutic dose, relative antimicrobial activity and extent of gastro-intestinal absorption when oral preparations are used.