Population Pharmacokinetics of Telapristone (CDB-4124) and its Active Monodemethylated Metabolite CDB-4453, with a Mixture Model for Total Clearance

Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n = 32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-order absorption and elimination adequately described the pharmacokinetics of telapristone and CDB-4453. Telapristone was rapidly absorbed with an absorption rate constant (Ka) of 1.26 h−1. Moderate renal impairment resulted in a 74% decrease in Ka. The population estimates for oral clearance (CL/F) for the two populations were 11.6 and 3.34 L/h, respectively, with 25% of the subjects being allocated to the high-clearance group. Apparent volume of distribution for the central compartment (V2/F) was 37.4 L, apparent inter-compartmental clearance (Q/F) was 21.9 L/h, and apparent peripheral volume of distribution for the parent (V4/F) was 120 L. The ratio of the fraction of telapristone converted to CDB-4453 to the distribution volume of CDB-4453 (Fmetest) was 0.20/L. Apparent volume of distribution of the metabolite compartment (V3/F) was fixed to 1 L and apparent clearance of the metabolite (CLM/F) was 2.43 L/h. A two-compartment parent-metabolite model adequately described the pharmacokinetics of telapristone and CDB-4453. The clearance of telapristone was separated into two populations and could be the result of metabolism via polymorphic CYP3A5

Nutritional supplement use by elite young UK athletes: fallacies of advice regarding efficacy

BACKGROUND: The objective was to study nutritional supplement use among young elite UK athletes to establish whether a rationale versus practice incongruence exists, and to investigate the sources of information. Survey data were analysed for association between supplements used and motives for using such substances among young athletes along with the sources of advice and literature precedents on supplement effects. METHODS: Participants were elite UK male and female athletes, within the age range between 12 and 21 (n = 403), mean age 17.66 +/- 1.99. Associations between type of supplements and reasons for using supplements were tested by calculating Pearson's chi2 and the strength of these symmetric associations shown by phi association coefficients. RESULTS: Single supplement use was reported by 48.1%, with energy drinks being the most popular, consumed by 41.7% of all athletes and 86.6% of the supplement users in the sample. No agreement was observed between athletes' rationale and behaviour in relation to nutritional supplements except for creatine. Among health professionals, nutritionists and physiotherapists, followed by coaches, were most frequently consulted. Answers regarding reasons and supplements used showed incongruence and suggest widespread misinformation regarding supplements and their effects is an issue for the young athlete. CONCLUSION: Widespread supplement taking behaviour was evidenced in the young elite athlete population with the most notable congruence between rationale and practice among young athletes being performance-related. Young athletes in the present sample appear to be less 'health conscious' and more 'performance focused' than their adult counterparts. Further research, using a full list of supplements, is warranted to test the hypothesis that health consciousness is less dominant in supplement choice by young athletes

Jahrbuch Netzpolitik 2012 : von A wie ACTA bis Z wie Zensur

The authors give a review on different aspects of internet governance in 2012