title: Pharmacokinetics of CS-866, a new angiotensin II receptor blocker, in healthy subjects.
abstract: CS-866, a novel angiotensin II receptor blocker, is rapidly and completely metabolized to RNH-6270, its active metabolite. The pharmacokinetics of RNH-6270 following oral CS-866 or intravenous RNH-6270 administration was determined in 104 healthy male volunteers. The pharmacokinetics of RNH-6270 was linear over dose ranges of 1 to 32 mg (intravenous RNH-6270 administration) and 10 to 160 mg (oral CS-866 administration). The time to maximum plasma concentration of RNH-6270 after oral CS-866 administration ranged from 1.4 to 2.8 hours, and the terminal elimination half-life ranged from 12 to 18 hours. Absolute bioavailability of RNH-6270 after oral administration of CS-866 was 26%. Administration of CS-866 once daily for 10 days did not result in drug accumulation. When administered intravenously, RNH-6270 has a volume of distribution of 15 to 25 L. Approximately 35% to 50% of RNH-6270 is excreted unchanged in the urine. CS-866 was safe and well tolerated at doses of up to 160 mg/day.
authors.affiliation: Sankyo Pharma Development, Edison, New Jersey 08837, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Schwocho
authors.forename: H N
authors.initials: HN
authors.lastname: Masonson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D057911:Angiotensin Receptor Antagonists; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000652:urine*; D007262:Infusions, Intravenous; D008099:Liver / Q000201:enzymology; D008297:Male; D008657:Metabolic Clearance Rate; D009140:Musculoskeletal Diseases / Q000139:chemically induced; D000068557:Olmesartan Medoxomil; D010146:Pain / Q000139:chemically induced; D013607:Tablets; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000652:urine*; D000637:Transaminases / Q000187:drug effects
chemical_list: D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D013607:Tablets; D013777:Tetrazoles; D000068557:Olmesartan Medoxomil; C437965:olmesartan; D000637:Transaminases