THE ENHANCEMENT OF CHLORTETRACYCLINE ABSORPTION BY CITRIC ACID

¹ Lederle Laboratories Division, American Cyanamid Company, Pearl River, New York

1. Enhanced chlortetracycline blood serum levels were observed in dogs four hours after the oral administration of 8:1 citric acid-chlortetracycline hydrochloride combinations. An effect also appeared demonstrable at the 4:1 ratio.

2. Twelve of the nineteen dogs treated with citric acid showed recoveries of unabsorbed chlortetracycline from the gastro-intestinal tract considerably less than expectation for chlortetracycline without citric acid. For all dogs the per cent recovery of administered dose was 38, contrasted with 59 per cent for chlortetracycline alone.

3. For equivalent amounts of chlortetracycline not recovered from the gastro-intestinal tract, the blood levels were definitely higher in the citric acid treated group. This is interpreted as indicative of an enhancement of chlortetracycline stability in the gastro-intestinal tract.

4. The action of citric acid appears to be confined to the gastro-intestinal tract. It has no effect on the rate of passage of chlortetracycline or on the distribution pattern.

5. From 5 to 25 mgm. per kgm., chlortetracycline absorption coefficients increased with the dose. At equivalent dose levels, they were usually greater in the presence of citric acid. Over the dose range investigated, the data indicate the absence of a limiting rate of chlortetracycline absorption from the gastro-intestinal tract of the dog.

6. The mechanism of action of citric acid is unknown. Possible factors are complexing with calcium and other metallic ions and enhancement of chlortetracycline stability.