The AUC0–∞ was calculated from the AUC0–1,590 VX-680 concentration by the addition of a constant (Cp/λz), where Cp is the last observed quantifiable concentration and λz is elimination rate constant. This was performed by dividing the Cp by λz determined using linear Flavopiridol manufacturer regression of Cp versus time data (standard extrapolation technique). The elimination rate constant and the corresponding elimination half-life was estimated by log-linear least squares regression of the terminal part of the plasma concentration versus time

curve. Absorption lag time (Tlag) is determined as the first time point with a measurable concentration in plasma. The demographic baseline levels of total and free testosterone, dihydrotestosterone, SHBG, and albumin were calculated by taking the mean of F1 and F2. For the baseline corrected pharmacokinetic parameters, the raw data of each subject was taken as baseline. Dependent on distribution of normality, paired-samples t tests were used for the difference between the F1 and F2 pharmacokinetic parameters for the

subjects of whom F1 and F2 data was obtained (n = 12). For all LXH254 in vivo analyses a (two-sided) p value <0.05 was considered statistically significant. Statistical analyses were conducted with SPSS 19.0 (IBM SPSS Statistics for Windows, Version 19.0. Armonk, NY: IBM Corp). 3 Results The baseline characteristics and hormone levels of the 13 study participants are outlined in Table 1. Because one subject discontinued after F1 dose, an additional subject was included into the study in order to have F1 and F2 data from 12 subjects. Therefore, 13 oxyclozanide subjects were included in F1 and 12 subjects were included in F2. Table 1 shows the baseline demographics of the 13 study participants, all subjects were Caucasian and the mean age was 25.8 years. Baseline levels (measured at screening) of testosterone, SHBG, and albumin were all in the normal

female range. Table 1 Baseline and clinical characteristics of the participants Characteristic Value (n = 13) Age (years) 25.8 ± 4.9 Race  Caucasian 13 BMI (kg/m2) 22.9 ± 2.1 Contraceptive  Hormonal 12   Combined oral contraceptive pill 8   IUD (levonorgestrel) 3   Vaginal ring (progestin and estrogen) 1  Non-hormonal 1 Total testosterone (ng/mL) 0.26 ± 0.1 SHBG (nmol/L) 92 ± 80 Albumin (g/L) 41.5 ± 2.8 Baseline levels of total testosterone, SHBG and albumin were measured at the screening visit The values are mean ± SD. To convert total testosterone to nanomoles per liter, multiply by 3.467 BMI body mass index, IUD intrauterine device, SHBG sex hormone-binding globulin 3.1 Pharmacokinetic Results 3.1.1 Testosterone, Free Testosterone and Dihydrotestosterone Pharmacokinetic results of the two administrations show that from both products, testosterone was rapidly absorbed with a total testosterone T max between 12 and 16 minutes (0.201–0.256 h) and a half-life between 36 and 44 minutes (0.598–0.726 h).