After a single oral dose of silodosin in male rats ， male dogs and healthy human male volunteers ， Cmax occurred with − in about 2 h ， indicating rapid absorption ． The elimination half − 1ife was about 2 h in rat and dog， but 4． 7 h (fasted)and 6． Oh (non − fasted)in humans ． Absolute bioavailability values in rat ， dog and human were about 9 ， 25 and 32 ％ ， respec − tive 且 y ， In rat and dog ， total blood clearance was almost equivalent to the hepatic blood flow ， but that in human was low (20 ％)， demonstrating a large species difference in hepatic clearance ． ln each species ， the apparent volume of distribu − tion exceeded the vo 【 ume of total body water ． After an oral dose of i4C ・ silodosin to male rats ， radioactivity was rapidly and widely distributed to most tissues ． The highest concentrations outside the gastrointestinal tract were found in liver and kidney， with only 且 ow concentrations in brain tissues ． The in vitro plasma protein binding of silodosin was about 80 ％ in rat and dog， and 95， 6％ in humans ， with α 1 − acid glycoprotein(AGP)contributing to the binding profile ． Silodosin was found to be a dual substrate for CYP3A4 and ρ 一 glycoprotein ． In human plasma ， two major metabolites generated by UDP − glucuronosyltransferase (UGT ；UGT2B7)and alcohol ／ aldehyde dehydrogenase (ADH ／ ALDH) were found ， but no glucuronide conjugates were detected in rat or dog plasma ． After a single oral dose of 且 4C − silodosin in rat ， dog and human ， the urinary excretion of radioactivity was 15 − 34 ％ ， with that of unchanged silodosin being less than 4 ％ ． The radioactivity was predominantly excreted via the feces ． Key werds − silodosin (KMD − 3213) ；orlA − adrenoceptor antagonist ；pharmacokinetics ；metabolism ；species differences

No abstract

No abstract

After a single oral dose of silodosin in male rats, male dogs and healthy human male volunteers, C max occurred within about 2 h, indicating rapid absorption. The elimination half-life was about 2 h in rat and dog, but 4.7 h (fasted) and 6.0 h (non-fasted) in humans. Absolute bioavailability values in rat, dog and human were about 9, 25 and 32％, respectively. In rat and dog, total blood clearance was almost equivalent to the hepatic blood ‰ow, but that in human was low (20％), demonstrating a large species diŠerence in hepatic clearance. In each species, the apparent volume of distribution exceeded the volume of total body water. After an oral dose of 14 C-silodosin to male rats, radioactivity was rapidly and widely distributed to most tissues. The highest concentrations outside the gastrointestinal tract were found in liver and kidney, with only low concentrations in brain tissues. The in vitro plasma protein binding of silodosin was about 80 ％ in rat and dog, and 95.6％ in humans, with a 1 -acid glycoprotein (AGP) contributing to the binding proˆle. Silodosin was found to be a dual substrate for CYP3A4 and p-glycoprotein. In human plasma, two major metabolites generated by UDP-glucuronosyltransferase (UGT; UGT2B7) and alcohol/aldehyde dehydrogenase (ADH/ALDH) were found, but no glucuronide conjugates were detected in rat or dog plasma. After a single oral dose of 14 C-silodosin in rat, dog and human, the urinary excretion of radioactivity was 15-34％, with that of unchanged silodosin being less than 4％. The radioactivity was predominantly excreted via the feces.

No abstract