In 1941 Abraham and his associates1 attempted to administer penicillin by the oral route and found that it was rapidly destroyed by the gastric acidity. These investigators employed phenyl salicylate coated capsules with relatively small doses of the drug but abandoned this method after unsuccessful trials. In corroboratory experiments Rammelkamp and Keefer2 also demonstrated that penicillin was inactivated by the hydrochloric acid in the stomach. However, following intraduodenal administration, fairly adequate penicillin concentrations were demonstrated in the blood, approximating those achieved after intramuscular injection. In this regard Rammelkamp and Helm3 gave a penicillin solution containing 20,000 Florey units by mouth to 2 patients with achlorhydria associated with pernicious anemia and observed that the blood concentrations of penicillin were greater than those assayed in normal subjects.
In all of these preliminary experiments in which the oral route was used, comparatively small doses, ranging between 10,000 and 20,000 units,
ROSS S, BURKE FG, McLENDON PA, Porter BV. PENICILLIN BY MOUTH: REPORT OF A CLINICAL TRIAL. JAMA. 1945;129(5):327–332. doi:10.1001/jama.1945.02860390013003
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