Pharmacokinetics and dose finding of a potent aromatase inhibitor, aromasin (exemestane), in young males.
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 Blood was withdrawn before and 24 h after the last dose of each treatment period.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 <or= 0.002); 50 mg, 32% (P <or= 0.008)], with a reciprocal increase in testosterone concentrations (60% and 56%; P <or= 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.
Mauras
Nelly
N
Nemours Children's Clinic and Research Programs, Jacksonville, Florida 32207, USA. nmuras@nemours.org
Lima
John
J
Patel
Deval
D
Rini
Annie
A
di Salle
Enrico
E
Kwok
Ambrose
A
Lippe
Barbara
B
D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D047072:Aromatase Inhibitors; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D009994:Osmolar Concentration; D012016:Reference Values; D012727:Sex Characteristics; D013739:Testosterone / Q000097:blood; D013997:Time Factors
D000730:Androstadienes; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D013739:Testosterone; D004958:Estradiol; C056516:exemestane