Absorption and excretion of colestilan in healthy subjects.

Colestilan, an anion-exchange resin binding both phosphate and bile-acid anions, is under development for the treatment of hyperphosphataemia and dyslipidaemia, which occur in the majority of end-stage renal disease patients. This study using 14C-colestilan was conducted to investigate the absorption and excretion of colestilan in humans. Following a 28-day run-in period with administration of colestilan 3 g three times daily, 12 subjects received a single oral dose of 14C-colestilan 100 mg (approximately 4.0 MBq) and colestilan 3 g under fasted conditions on the morning of day 1. A total of 9 g of colestilan was administered three times daily on days 1-4. Total radioactivity levels in whole blood (at 4, 8, 12 and 24 hours and then at 24-hour intervals) and in the urine and faeces (from 0 to 24 hours and then at 24-hour intervals) were monitored up to 216 hours postdose (day 10). Total radioactivity measured in all whole-blood samples was below the lower limit of quantification (0.025 microg equivalent of 14C-labelled colestilan/mL of whole blood). Total radioactivity assessed in all urine samples was also below the lower limit of quantification (0.003 microg equivalent/mL for urine), except at 0-24 hours postdose, when 0.01% of the radioactive dose was excreted by all subjects. This level was below the predetermined water soluble impurity level of 0.04%. The mean cumulative excretion of total radioactivity in the faeces was 99.66% by 216 hours postdose, excluding one subject with incomplete collection of faecal samples. These results demonstrate that colestilan is not absorbed from the gastrointestinal tract and is completely excreted in the faeces.

Effects of oral administration of androstenedione on plasma androgens in young women using hormonal contraception.

Androstenedione as a dietary supplement has been targeted at the sporting community, but there are limited data regarding its effects on plasma androgens in young women. A double-blind, cross-over study was undertaken involving 10 women (20-32 yr) using hormonal contraception. Because contamination of supplements has been reported, an in-house oral formulation was prepared containing purified androstenedione, the control being lactose only. After oral administration of a single dose of androstenedione (100 mg), blood was collected frequently up to 8 h and at 24 h. Maximum plasma androgen concentrations observed between volunteers were well above the upper limit of reference ranges for women, being 121-346 nmol/liter for androstenedione, 14-54 nmol/liter for testosterone (T), 11-32 nmol/liter for 5alpha-dihydrotestosterone, and 23-90 nmol/liter for 3alpha-androstanediol glucuronide. The free androgen index and T concentration changed in a similar manner. The mean change in area under the plasma concentration-time curve (0-24 h), compared with control data were: androstenedione approximately 7-fold, T approximately 16-fold, 5alpha-dihydrotestosterone approximately 9-fold, and 3alpha-androstanediol glucuronide approximately 5-fold; the mean conversion ratio of androstenedione to T was 12.5% (range 7.8-21.6%). Increases in T area under the plasma concentration-time curve were correlated with SHBG concentration (r = 0.80; P = 0.005). Formulation characteristics and SHBG levels appear to be important factors when considering plasma androgen increases after acute androstenedione administration.