title: Pharmacokinetics and acute safety of inhaled testosterone in postmenopausal women.
abstract: This was a preliminary feasibility study to assess the pharmacokinetics and acute safety of a single dose of orally inhaled testosterone via the AERx system, a novel handheld aerosol delivery system in postmenopausal women. Twelve postmenopausal women stabilized on oral estrogen therapy were treated with a single dose of testosterone (0.1, 0.2, or 0.3 mg) by inhalation. Plasma concentrations of sex steroids were measured between 1 and 360 minutes. Pulmonary and cardiovascular adverse events were monitored. Inhaled testosterone produced a dose-dependent increase in plasma total and free testosterone. At the highest dose (0.3 mg), total and free testosterone increased from baseline (mean +/- SD, 0.6 +/- 0.3 nmol/L, 2.5 +/- 1.0 pmol/L) to maximum levels of 62.6 +/- 20.4 nmol/L (total) and 168.2 +/- 50.2 pmol/L(free), occurring 1 to 2 minutes after dosing. A 2-compartment model best described the free and total testosterone pharmacokinetic profile. Dihydrotestosterone levels were higher than baseline at 60 minutes (P < .0002). Estradiol did not vary, but sex hormone binding globulin and albumin fell. There were no adverse events related to the treatment. Administration of inhaled testosterone is safe and achieves a supraphysiologic "pulse" kinetic profile of total and free testosterone with a rapid return to pretreatment levels.
authors.affiliation: Jean Hailes Foundation, 173 Carinish Road, Clayton, Victoria, Australia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Davison
authors.forename: John
authors.initials: J
authors.lastname: Thipphawong
authors.forename: Jim
authors.initials: J
authors.lastname: Blanchard
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
authors.forename: Richard
authors.initials: R
authors.lastname: Morishige
authors.forename: Igor
authors.initials: I
authors.lastname: Gonda
authors.forename: Jerry
authors.initials: J
authors.lastname: Okikawa
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adams
authors.forename: Allan
authors.initials: A
authors.lastname: Evans
authors.forename: Babatunde
authors.initials: B
authors.lastname: Otulana
authors.forename: Susan
authors.initials: S
authors.lastname: Davis
mesh_terms: D000280:Administration, Inhalation; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003371:Cough / Q000139:chemically induced; D013196:Dihydrotestosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D018579:Patient Selection; D017698:Postmenopause / Q000187:drug effects* / Q000502:physiology; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D013997:Time Factors; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D013739:Testosterone