DETERMINATION OF AMPHOTERICIN B CONTENTIN THE BLOOD AND VISCERA OF RABBITS RECEIVING A LONG-TERM TOPICAL ADMINISTRATION WITH AN ATTEMPT TO CHECK CHRONIC TOXICITY
1970 Volume 18 Issue 2 Pages 129-132
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1970 Volume 18 Issue 2 Pages 129-132
In an attempt to check a possibility of absorption of amphotericin B from the skin tissue and the consequent induction of chronic toxicity when applied topically for a long period to laboratory animals, the antibiotic content in the blood and various organs were determined by a microbiological assay method devised by the authors which had been described in the preceding paper.
A micropulverized preparation of the antibiotic suspended in olive oil was administered onto the well-shaved skin in the back of rabbits with a dimension of ca. 5 cm × 5 cm. The suspension was given at the rate of 6 mg and 60 mg, respectively, every 24 hours for 4 weeks to each rabbit of the two groups consisting of five males each. Blood was collected every one week, and organs (liver, spleen and kidneys) were taken out immediately after the final collection of blood. These materials were applied to determination of amphotericin B content by a turbidity method using a strain of Candida albicans; the lower limit in an established determination standard curve was 0.003mcg/ml. The results obtained are as follows.
All the animals of the both groups were found to be below the lower limit of the antibiotic content in all the blood and three organs. During the whole period of observation, all were healthy, showing a normal increase in body weight. Neither any general and local symptoms nor any macroscopic pathological changes in all the organs including the above three were noticed.
These results present an evidence that, even when continuously given topically for a long term in a relatively large dose, amphotericin B cannot penetrate through the healthy skin tissue to distribute into the blood stream and organs in demonstrable amounts at least, and, in consequence, does not exhibit any serious general and local side effects. Thus, a possibility that this antibiotic might induce chronic toxicity would be denied in case of topical use at least.
