Silodosin
Silodosin (known by the trade names Urief in Japan, Rapaflo in North America, and Silodyx or Niksol in the European Union) is a medication for the symptomatic treatment of benign prostatic hyperplasia (BPH). It acts as an α-adrenoceptor antagonist with high uroselectivity (selectivity for the prostate). Medical uses. Silodosin is used for the treatment of BPH in adult men. Contraindications. According to European labels, silodosin has no contraindications apart from known hypersensitivity. Another source names recurring urinary retention, recurring urinary infections, uncontrolled macrohematuria, bladder stones, hydronephrosis, combination with other α-antagonists or dopamine agonists, and severe renal or  hepatic impairment as contraindications. Side effects. The most common adverse effect is loss of seminal emission. This seems to be caused by silodosin's high selectivity for α receptors. Other common adverse effects (in more than 1% of patients) are dizziness, orthostatic hypotension, diarrhoea, and clogged nose. Less common (0.1–1%) are tachycardia (fast heartbeat), dry mouth, nausea, skin reactions, and erectile dysfunction. Hypersensitivity reactions occur in fewer than 0.01% of patients. There have been reports about intraoperative floppy iris syndrome during cataract extractions. These side effects are similar to those of other α antagonists. Interactions. Combining silodosin with strong inhibitors  of the liver enzyme CYP3A4, such as ketoconazole, significantly increases its concentrations in the blood plasma and its area under the curve (AUC). Less potent CYP3A4 inhibitors such as diltiazem have a less pronounced effect on this parameters, which is not considered clinically significant. Inhibitors and inducers of the enzyme UGT2B7, alcohol dehydrogenases, and aldehyde dehydrogenases, as well as the transporter P-glycoprotein (P-gp), may also influence silodosin concentrations in the body. Digoxin, which is transported by P-gp, is not affected by silodosin; this means that silodosin does not significantly inhibit or induce P-gp. No relevant interactions  with antihypertensive drugs or with PDE5 inhibitors have been found in studies; although combination with other α-antagonists is not well studied. Pharmacology. Mechanism of action. Silodosin has high affinity for the α adrenergic receptor in the prostate, the bladder, and the prostatic urethra. By this mechanism it relaxes the smooth muscle in these organs, easing urinary flow and other symptoms of BPH. Pharmacokinetics. The absolute bioavailability after oral intake is 32%. Food has little effect on the AUC. When in the bloodstream, 96,6% of the substance are bound to blood plasma proteins. Its main metabolite is silodosin glucuronide, which  inhibits the α receptor with 1/8 of the affinity of the parent substance. 91% of the glucuronide are bound to plasma proteins. The enzyme mainly responsible for the formation of the glucuronide is UGT2B7. Other enzymes involved in the metabolism are alcohol dehydrogenases, aldehyde dehydrogenases and CYP3A4. Silodosin is almost completely excreted in the form of metabolites; 33.5% via the urine and 54.9% via the feces. The biological half-life of silodosin is 11 hours on average, and that of the glucuronide is 18 hours or 24 hours. (Sources are contradictory on this.) History. Silodosin received its first marketing approval  in Japan in May 2006, under the brand name "Urief", which is jointly marketed by Kissei Pharmaceutical and Daiichi Sankyo. Kissei licensed the US, Canadian, and Mexican rights for silodosin to Watson Pharmaceuticals (now Allergan) in 2004. The United States Food and Drug Administration and Health Canada approved silodosin under the brand name "Rapaflo" on 9 October 2008 and 11 January 2011, respectively. Society and culture. Brand names. Other brand names include "Urorec" (European Union), "Niksol" (Croatia), "Silorel" (Jamaica), "Sildoo", "Silodal", "Silodosia", "Silofast" (India) "Thrupas" (South Korea), "Flopadex" (Egypt), and "Urorec" (Russia). Research. As α adrenoceptor antagonists are being investigated  as a means to male birth control due to their ability to inhibit ejaculation but not orgasm, a trial with 15 male volunteers was conducted. While silodosin was completely efficacious in preventing the release of semen in all subjects, 12 out of the 15 patients reported mild discomfort upon orgasm. The men also reported the psychosexual side effect of being strongly dissatisfied by their lack of ejaculation.