Pharmacokinetics of CS-866, a new angiotensin II receptor blocker, in healthy subjects

J Clin Pharmacol. 2001 May;41(5):515-27. doi: 10.1177/00912700122010393.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Angiotensin Receptor Antagonists*
  • Area Under Curve
  • Biological Availability
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Humans
  • Hypotension / chemically induced
  • Imidazoles / administration & dosage
  • Imidazoles / adverse effects
  • Imidazoles / blood*
  • Imidazoles / urine*
  • Infusions, Intravenous
  • Liver / enzymology
  • Male
  • Metabolic Clearance Rate
  • Musculoskeletal Diseases / chemically induced
  • Olmesartan Medoxomil
  • Pain / chemically induced
  • Tablets
  • Tetrazoles / administration & dosage
  • Tetrazoles / adverse effects
  • Tetrazoles / blood*
  • Tetrazoles / urine*
  • Transaminases / drug effects

Substances

  • Angiotensin Receptor Antagonists
  • Imidazoles
  • Tablets
  • Tetrazoles
  • Olmesartan Medoxomil
  • olmesartan
  • Transaminases