THE INFLUENCE OF THE DOSAGE REGIMEN ON THE THERAPEUTIC ACTIVITY OF PENICILLIN G

¹ Christ Hospital Institute of Medical Research, Cincinnati, Ohio

A quantitative study has been made of the effectiveness of different dosage regimes of penicillin G against a fulminating pneumococcal infection in the white rat. The results of this study have shown that with treatment of brief duration (eight hours or less) two doses of sodium penicillin G administered two or four hours apart were significantly more effective than a single dose or two doses separated by an 8-hour interval. Likewise, when treatment was of moderate duration (96 hours or the equivalent), divided doses of sodium penicillin G administered at 2-, 4-, or 8-hour intervals were far more effective than divided doses at 12- or 24-hour intervals. It was also found that procaine penicillin G administered at 24-hour intervals was significantly more effective than sodium penicillin G given at these times, but not as effective as the sodium salt administered at 2-, 4-, or 8-hour intervals.

Measurements were also made of the concentrations of "penicillin" present in plasma after administration of equally effective doses of sodium or procaine penicillin G on the various dosage regimes. These measurements show that these equally effective doses maintained inhibitory concentrations of "penicillin" in plasma for only a small fraction of the dosage interval.

Although the above findings show that the effectiveness of penicillin therapy is related to the frequency of treatment, they offer no support for the general assumption that the effectiveness of therapy is dependent upon continued maintenance of inhibitory concentrations of the drug in body fluids. Rather they indicate that optimum therapeutic results, even in fulminating infections, may be achieved by administration of water-soluble penicillin salts at fairly widely spaced intervals.

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