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Article
January 1946

DYNAMICS OF THE ACTION OF PENICILLIN IN EXPERIMENTAL ANIMALSObservations on Mice

Arch Intern Med (Chic). 1946;77(1):1-15. doi:10.1001/archinte.1946.00210360006001
Abstract

I N THE last few years penicillin has established itself as a drug of great therapeutic value, possessing in a high degree the characteristics of an ideal antiseptic: exceedingly low toxicity and high bactericidal and bacteriostatic efficiency. The great demand for this drug in wartime and the early difficulties of large scale production made it imperative to use the minimal effective dosage. Arbitrary dosage schedules were selected by clinical trial and notable successes were achieved, but there is little evidence to show that the dosage used was optimal or even the most economical.

Early systematic studies1 demonstrated that penicillin is rapidly excreted in the urine after parenteral administration. It has been generally accepted in the past that a sustained blood level of the drug is essential and, therefore, that it must be administered either continuously or at frequent intervals or that special methods must be used to retard its

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