title: Pharmacoscintigraphy confirms consistent tamsulosin release from a novel triple-layered tablet.
abstract: Conventional modified release preparations of tamsulosin HCl have been linked to increased incidence of cardiovascular adverse events, possibly due to rapid drug peaks soon after ingestion. A 'flattened' absorption profile has been shown to reduce the occurrence of these unwanted effects while improving symptom control. The potential of a novel triple-layered tablet to effect prolonged release and continuous absorption of tamsulosin HCl in the gastrointestinal tract was investigated in this clinical study. Gastrointestinal (GI) transit behaviour was monitored by scintigraphic imaging of technetium-labelled tablets. Drug absorption levels were simultaneously determined through pharmacokinetic analysis of blood samples. A mean Cmax of 6 ± 3 ng/nL was achieved after 324 ± 184 min (mean tmax). The mean AUC0-24 was noted as 4,359 ± 1,880 ng/mL min. The mean gastric emptying and colon arrival times of the tablets were 105.2 ± 68.9 and 270.1 ± 32.0 min post-dose; giving a mean small intestine transit time of 164.9 ± 83.6 min. Variations in gastrointestinal transit did not appear to influence drug absorption. Correlation of scintigraphic and PK data indicated that tamsulosin HCl is released steadily throughout the entire GI tract, suggesting that the mechanism of drug release is independent of GI site allowing drug release even in the low moisture environment of the colon.
authors.affiliation: Bio-Images Research Ltd., Within Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK. leeann.hodges@bio-images.co.uk
authors.forename: L A
authors.initials: LA
authors.lastname: Hodges
authors.forename: K A
authors.initials: KA
authors.lastname: Sime
authors.forename: L A
authors.initials: LA
authors.lastname: Creech
authors.forename: S M
authors.initials: SM
authors.lastname: Connolly
authors.forename: S T
authors.initials: ST
authors.lastname: Barclay
authors.forename: Min Chang
authors.initials: MC
authors.lastname: Kwon
authors.forename: Byeong Jin
authors.initials: BJ
authors.lastname: Jeon
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Shim
authors.forename: Hun Sik
authors.initials: HS
authors.lastname: Wang
authors.forename: H N E
authors.initials: HN
authors.lastname: Stevens
authors.forename: Jun Sang
authors.initials: JS
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D041981:Gastrointestinal Tract / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005772:Gastrointestinal Transit; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011877:Radionuclide Imaging; D012606:Scotland; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013607:Tablets; D000077409:Tamsulosin; D013678:Technology, Pharmaceutical / Q000379:methods; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D013449:Sulfonamides; D013607:Tablets; D000077409:Tamsulosin
keywords: GLARS tablet; Gamma scintigraphy; Gastrointestinal transit; Tamsulosin hydrochloride