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

• Published in: The journal of clinical endocrinology and metabolism Vol. 88; no. 12; pp. 5951 - 5956
• Main Authors: Mauras, Nelly, Lima, John, Patel, Deval, Rini, Annie, di Salle, Enrico, Kwok, Ambrose, Lippe, Barbara
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.12.2003; Copyright by The Endocrine Society
• Subjects: Absorption; Administration, Oral; Adolescent; Adult; Androstadienes - administration & dosage; Androstadienes - chemistry; Androstadienes - pharmacokinetics; Aromatase Inhibitors; Biological and medical sciences; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacokinetics; Estradiol - blood; Estrogen Antagonists - administration & dosage; Estrogen Antagonists - chemistry; Estrogen Antagonists - pharmacokinetics; Half-Life; Hormones. Endocrine system; Humans; Male; Medical sciences; Osmolar Concentration; Pharmacology. Drug treatments; Reference Values; Sex Characteristics; Testosterone - blood; Time Factors; Antineoplastic agent; Steroid; Human; Healthy subject; Enzyme; Toxicity; Estrogen; Enzyme inhibitor; Estrogen synthase; Exemestane; Insulin like growth factor 1; Estradiol; Posology; Androstane derivatives; Biological activity; Blood plasma; Assay; Randomization; Lipemia; Adolescent; Young adult; Secondary effect; Pharmacokinetics
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2003-031279

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 Blood was withdrawn before and 24 h after the last dose of each treatment period.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.