The results of the pharmacokinetic study of the combination of testosterone and sildenafil will be described separately. At frequent time points, plasma samples were taken and the following pharmacokinetic parameters were determined: the time to maximum concentration (T max), half-life (T ½ ), maximum concentration

(C max), and area under the curve (AUC) for total testosterone, free testosterone, buspirone, and buspirone’s main metabolite (1-(2-pyrimidinyl)-piperazine) for each formulation. 2 Methods 2.1 Study Subjects Eligible women were aged between 18 and 35 years, premenopausal, and had a body mass index (BMI) VX-680 cell line between 18 and 30 kg/m2. Exclusion criteria included an endocrine disease,

neurological problems, a cardiovascular condition, hypertension, abnormal liver or renal function, and a history of a hormone-dependent Selleck TGFbeta inhibitor malignancy. Women taking medications that interfere with the metabolism of sex steroids (e.g., oral contraceptives containing anti-androgens or (anti)androgenic progestogens), or who used serotonergic drugs or who had used testosterone therapy within 6 months before study entry were also excluded. Women were recruited and enrolled from advertisements, and via a Erismodegib database of a contract research organization (QPS in the Netherlands). Recruitment started in June 2012 and the study was ended in November 2012. To determine eligibility, participants were screened approximately 4 weeks prior to study entry. In addition to an assessment of medical history, all subjects received a physical examination including a 12-lead electrocardiogram, standard biochemistry, serology, and hematological laboratory tests. Blood samples for determination of baseline levels of total testosterone, sex hormone-binding globulin (SHBG), albumin, thyroid-stimulating hormone (TSH), follicle-stimulating

hormone (FSH) and estrogen were collected at the screening visit. A urine pregnancy test ADP ribosylation factor was applied to all women. Thirteen healthy young women participated after providing written informed consent. This study was approved by the local medical ethics committee (Stichting BEBO, Assen, the Netherlands) and carried out in agreement with the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP). 2.2 Study Design This was a single-center, investigator-blind, randomized, cross-over controlled study investigating two different modes of administration of a combination of testosterone and buspirone. The first mode (F1) consisted of the administration of a sublingual solution containing testosterone (0.5 mg) complexed with cyclodextrin, followed 2.5 hours later by an orally administered tablet containing 10 mg buspirone hydrochloride in a gelatin capsule.