[Pharmacokinetics and disposition of silodosin (KMD-3213)].
Article Details
- CitationCopy to clipboard
Matsubara Y, Kanazawa T, Kojima Y, Abe Y, Kobayashi K, Kanbe H, Harada H, Momose Y, Terakado S, Adachi Y, Midgley I
[Pharmacokinetics and disposition of silodosin (KMD-3213)].
Yakugaku Zasshi. 2006 Mar;126 Spec no.:237-45.
- PubMed ID
- 16518089 [ View in PubMed]
- 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 flow, but that in human was low (20%), demonstrating a large species difference 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 alpha(1)-acid glycoprotein (AGP) contributing to the binding profile. 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Silodosin Cytochrome P450 3A4 Protein Humans UnknownSubstrateDetails - Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Silodosin Multidrug resistance protein 3 Protein Humans UnknownSubstrateDetails Silodosin P-glycoprotein 1 Protein Humans UnknownSubstrateDetails - Drug Reactions
Reaction Details Details Details Details Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareSilodosinFluconazole The excretion of Silodosin can be decreased when combined with Fluconazole. SilodosinErythromycin The excretion of Silodosin can be decreased when combined with Erythromycin. SilodosinSildenafil The excretion of Silodosin can be decreased when combined with Sildenafil. SilodosinReserpine The excretion of Silodosin can be decreased when combined with Reserpine. SilodosinSorafenib The excretion of Silodosin can be decreased when combined with Sorafenib.
