Pharmacokinetics and pharmacodynamics of anastrozole in pubertal boys with recent-onset gynecomastia.
BACKGROUND
Use of aromatase inhibitors to suppress estrogen production is being actively investigated in a variety of experimental conditions in both females and males. Anastrozole (Arimidex) is a potent and selective reversible inhibitor of the aromatase enzyme in females.


OBJECTIVE
Our objective was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of anastrozole in adolescent males with gynecomastia of less than 1 yr duration. The effect of anastrozole on breast size was also assessed as an exploratory aim.


METHODS
We conducted a PK/PD open-label study.


METHODS
This clinical research center study was undertaken at pediatric academic centers.


METHODS
Forty-two boys with gynecomastia (mean age 13 +/- 1.8 yr; duration of gynecomastia 7.0 +/- 2.5 months; body mass index 28.3 +/- 5.9 kg/m(2)) were recruited.


METHODS
Anastrozole, 1 mg, was given daily for 6 months.


RESULTS
We assessed PK/PD of anastrozole after 14 d daily dosing and changes in breast size (exploratory aim) by manual tape measurements (area) and ultrasound (volume) after 6 months.


RESULTS
Anastrozole was rapidly absorbed orally (time to reach maximum concentration, 1 h) with a slow apparent clearance of 1.54 liters/h and a terminal half-life of 46.8 h. Testosterone/estradiol ratios increased significantly with concomitant increase in LH/FSH concentrations indicating aromatase blockade. There was a reduction in breast area (approximately 63%) and breast volume (approximately 57%) in the study group as compared with baseline (P = 0.004). The drug was well tolerated.


CONCLUSIONS
Anastrozole is a potent aromatase inhibitor in adolescent males, with rapid absorption and slow elimination kinetics after oral dosing. Exploratory analysis of changes in breast size showed breast reduction in the cohort; this deserves further study.
Mauras
Nelly
N
Nemours Children's Clinic, 807 Children's Way, Jacksonville, FL 32207, USA. nmauras@nemours.org
Bishop
Kim
K
Merinbaum
Debbie
D
Emeribe
Ugochi
U
Agbo
Felix
F
Lowe
Elizabeth
E
D000293:Adolescent; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000254:growth & development; D002648:Child; D006177:Gynecomastia / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009570:Nitriles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011627:Puberty / Q000378:metabolism*; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole