Binding of mepartricin to sex hormones, a key factor of its activity on benign prostatic hyperplasia.
Androgens and estrogens, mainly testosterone (TES) and dihydrotestosterone (DHT) and 17 beta-estradiol (EST), are widely recognized to regulate the prostate growth and their imbalance with aging, leading to reduction of androgens and relative increase of estrogens, may be responsible for the development of benign prostatic hyperplasia (BPH). Mepartricin (CAS 11121-32-7), a polyene drug for medical treatment of BPH, was assayed in vitro for its ability to bind with 14C-labelled sex hormones, by incubation in buffered saline, serum and bile, followed by centrifugation and dosing of the radioactivity in the supernatant. It proved effective in complexing up to 90% of TES and DHT in buffered saline and up to 80% of EST in bile. Due to minimal absorption of oral mepartricin and to much higher enterohepatic circulation for estrogens than for androgens, the binding effect of mepartricin on EST in the gut should be of particular pharmacological relevance to explain its mechanism of action on BPH.
Barone
D
D
LCG-RBM, Laboratories & Clinics Group, Ricerche Biomediche Antoine Marxer S.p.A., Colleretto Giacosa, Turin, Italy.
Peroglio
F
F
Toso
E
E
Bruzzese
T
T
D000818:Animals; D001646:Bile / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002417:Cattle; D002498:Centrifugation; D013196:Dihydrotestosterone / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005704:Gallbladder / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006727:Hormone Antagonists / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008613:Mepartricin / Q000378:metabolism* / Q000627:therapeutic use*; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism*; D011485:Protein Binding; D013739:Testosterone / Q000378:metabolism
D001798:Blood Proteins; D012739:Gonadal Steroid Hormones; D006727:Hormone Antagonists; D013196:Dihydrotestosterone; D008613:Mepartricin; D013739:Testosterone; D004958:Estradiol