ABSORPTION AND EXCRETION OF AMPHOTERICIN B IN VOLUNTEERS AND PATIENTS AFTER ORAL ADMINISTRATIONS

Abstract

An attempt was made to study absorption and excretion of amphotericin B in healthy male adult volunteers and patients with chronic pulmonary diseases such as tuberculosis or mycosis following a single oral administration in the form of tablet and syrup.
For determination of amphotericin B concentration in body fluid and feces, the turbidity method was employed by using Candida albicans Shibuya strain with sensitivity ranging from 0.01 to 0.2 mcg/ml. Fecal samples for determination were prepared by homogenizing the feces collected during every 24 hours by the addition of phosphate buffer of pH 6. 2. Thereafter, the samples were lyophilized and then extracted overnight by adding 100% dimethylsulfoxide. In vitro recovery rate of amphotericin B from positive control was 75%.
In the above volunteers and patients, antifungal activity of amphotericin B failed to be traced in serum samples during the course of experiment following a single oral administration at a dose of 35 mg/kg body weight. No traces of the activity were detected except in two of fifteen urine samples collected during the first 24 hours after the administration.
During the four-day period following the administration of amphotericin B to the volunteers and patients, the rate of recovery in feces reached 28%-78% and 15%-86% respectively. It was learned, however, that the excretion takes place mostly within the first three days following the administration. These results seem to give an evidence to the clinical efficacy of amphotericin B in suppressing an overgrowth of Candida and other yeasts in the gastrointestinal tract and subsequent infections.
During the study, no side reaction was noticed whatsoever could be attributable to the drug or necessitated discontinuation of administration.