No abstract

Apremilast is a novel, orally available small molecule that specifically inhibits PDE4and thus modulates multiple pro- and anti-inflammatory mediators, and is currently under clinical development for the treatment of psoriasis and psoriatic arthritis.The pharmacokinetics and disposition of [14C]apremilastwas investigated following a single oral dose (20 mg, 100 uCi) to healthy male subjects.Approximately 58% of the radioactive dose was excreted in urine, while faeces contained 39%. Mean Cmax, AUC0 and tmax values for apremilast in plasma were 333 ng/mL, 1970 ng*h/mL and 1.5 h. Apremilast was extensively metabolized via multiple pathways, with unchanged drug representing 45% of the circulating radioactivity and <7% of the excreted radioactivity.The predominant metabolite was O-desmethyl apremilast glucuronide, representing 39% of plasma radioactivity and 34% of excreted radioactivity. The only other radioactive components that represented >4%of the excreted radioactivity were O-demethylated apremilast and its hydrolysis product. Additional minor circulating and excreted compounds were formed via O-demethylation, O-deethylation, N-deacetylation, hydroxylation, glucuronidation and/or hydrolysis. The major metabolites were at least 50-fold less pharmacologically active than apremilast. Metabolic clearance of apremilast was the major route of elimination, while non-enzymatic hydrolysis and excretion of unchanged drug were involved to a lesser extent.

The cumulative recovery data in urine and feces are consistent with the conclusion that colesevelam is not absorbed and is excreted entirely through the gastrointestinal system.

No abstract

Three human cell lines (glioma, melanoma and fibroblast) were evaluated for responses to low dose-rate irradiation (LDRI) (0.88 and 0.41 cGy per min) alone or with concurrent heating (41 degrees C) during irradiation. In order to avoid cell cycle redistribution cells were held in plateau phase. The results show that the lowest LDRI gave maximum sparing in the glioma and the fibroblast cell lines while both dose rates achieved approximately the same effect in the melanoma line. The melanoma line was the most heat sensitive and showed the greatest thermal enhancement ratio (TER). For all cell lines TER was greatest at the lowest dose-rate, and in the melanoma the heat plus LDRI curve gave lower survival than the high dose-rate irradiation survival curves. These data show that concurrent mild hyperthermia combined with LDRI used in brachytherapy can enhance the effectiveness of clinical brachytherapy treatments. In addition, this effect was largest in the most resistant cell line indicating the potential for using this combination to overcome radioresistance in brachytherapy.