The Low Therapeutic Activity of Penicillin K Relative to That of Penicillins F, G, and X, and Its Pharmacological Basis.

One hour after the injection into rabbits or man of penicillins F, G, K, and X at 0.6 mg./kg., blood levels of K were one-fourth to one-eleventh of those observed with the other penicillins, and K persisted at demonstrable levels for relatively short periods. In both rabbits and man the recovery of K in the urine averaged 30-35 per cent. This compares with an average recovery for F, G, and X of 74 per cent in rabbits and 91 per cent in man. In the treatment of experimental pneumococcal infections in white mice, an impure preparation of K was one-sixth as active as G and one-eighth as active as X. In the treatment of experimental streptococcal infections in white mice, a pure preparation of K was one-eleventh as active as G, and one-thirtieth as active as X. The above data suggest that penicillin K is inactivated in the body to a greater extent and more rapidly than either F, G, or X, resulting in a far lower therapeutic activity than would be anticipated from its bactericidal action in vitro. It seems clear that the amount of K in commercial penicillin should be minimized; and it would seem desirable to standardize impure mixtures of penicillins for therapeutic use by some method other than their bactericidal activity in vitro.