The effect of polyene macrolides on the prostate gland and canine prostatic hyperplasia.

Abstract

Candicidin,1-2 one of the polyene macrolide antifungal antibiotics, has been known for 15 years as a poltent and effective therapeutic agent active against a wide variety of yeast and fungi, including numerous animal pathogens. Produced by a strain of Streptormyces griseus isolated in 1948, the first in vivo evaluation of candicidin3 was made in 1953. As is characteristic of all polyene macrolide antifungal antibiotics, candicidin is far less toxic by oral administration than by parenteral routes. Generally, very little, if any, absorption from the gastrointestinal tract is believed t;o occur. As a result, most clinical applications of these antibiotics are largely limited to topical use including the vaginal area. The sole oral application of these antibiotics to date has been the treatment of yeast and fungal infections of the intestinal tract. In a series of studies designed to determine the extenit anid nature of the oral toxicity of candicidin in dogs and other laboratory animals, a rather interesting observation was made. With daily oral administration of candicidin at doses of 20 mg/kg of body weight and higher for periods of 30 days and more, examinationi of different body organs at autopsy indicated that one principal reaction was an apparent reduction in the size of the prostate gland. This preliminary observation of the effect of orally administered candicidin on the prostate gland volume stimulated further investigat;ions to determine the possible effects of candicidin and related polyene macrolides on canine prostatic glandular hyperplasia. The results of these studies are reported here. In cases of old dogs with benign prostatic hypertrophy, confirmed by pretreatment needle-punch biopsy at laparotomy followed by histological examination, oral treatment with a variety of tetraene, pentaene, and heptaene macrolides produced marked reductions in the texture and volume of the glands. The heptaene macrolides, candicidin and amphotericin B, in particular, produced posttreatment needle-punc:h biopsies exhibiting marked histological changes involving diminutions of gland diameters and epithelial cell heights associated with reduced congestion, granularity, and papillations. It is suggested that the polyene macrolide antifungal antibiotics as a class may be active for the treatment of prostatic hypertrophy by oral route. Materials and Methods.-Mongrel dogs, destined for the pound, preselected oil the basis of age (approximately 7-15 years) and of the possibility of the presence of prostatic glandular hyperplasia as iniitially determined by rectal palpation, were obtained for these studies. The dogs were acclimatized to kennel conditions for 7 days. Final selection for experiment was made after surgical examination by laparotomy to establish the hypertrophic condition of the prostate glands. Anesthesia was induced by myothesia (sodium secobarbital and mephenesin, 5:3). The prostate glands were exposed by a midliie abdominal inicision from the pubis to the umbilicus. The peritoneum was entered,