Pharmacokinetics and Dose Finding of a Potent Aromatase Inhibitor, Aromasin (Exemestane), in Young Males

Abstract

Abstract Suppression of estrogen, via estrogen receptor or aromatase blockade, is being investigated in the treatment of different conditions. Exemestane (Aromasin) is a potent and selective irreversible aromatase inhibitor. To characterize its suppression of estrogen and its pharmacokinetic (PK) properties in males, healthy eugonadal subjects (14–26 yr of age) were recruited. In a cross-over study, 12 were randomly assigned to 25 and 50 mg exemestane daily, orally, for 10 d with a 14-d washout period. Blood was withdrawn before and 24 h after the last dose of each treatment period. A PK study was performed (n = 10) using a 25-mg dose. Exemestane suppressed plasma estradiol comparably with either dose [25 mg, 38% (P ≤ 0.002); 50 mg, 32% (P ≤ 0.008)], with a reciprocal increase in testosterone concentrations (60% and 56%; P ≤ 0.003 for both). Plasma lipids and IGF-I concentrations were unaffected by treatment. The PK properties of the 25-mg dose showed the highest exemestane concentrations 1 h after administration, indicating rapid absorption. The terminal half-life was 8.9 h. Maximal estradiol suppression of 62 ± 14% was observed at 12 h. The drug was well tolerated. In conclusion, exemestane is a potent aromatase inhibitor in men and an alternative to the choice of available inhibitors. Long-term efficacy and safety will need further study.