title: Pharmacokinetic and pharmacodynamic comparison of an osmotic release oral metoprolol tablet and the metoprolol conventional tablet.
abstract: Four double-blind, Latin-square studies were conducted to compare the pharmacokinetics and pharmacodynamic bioavailability of metoprolol OROS (oral osmotic) and the conventional tablet (CT) of metoprolol. Metoprolol OROS (7/95 mg or 14/190 mg) was administered once daily in doses equivalent to 100 mg of metoprolol CT given once, twice, thrice, and four times a day. In all four studies, lower peak plasma concentrations and longer times to peak were observed after metoprolol OROS than after metoprolol CT, indicating a controlled-release profile for metoprolol OROS. beta-Adrenergic blockade, as measured by reductions in exercise heart rate, was lower after metoprolol OROS than after metoprolol CT, but metoprolol OROS provided a smoother and more sustained beta-blockade. All four doses of metoprolol OROS at steady state produced relative pharmacodynamic bioavailability that ranged from 87% to 104% of that produced by equivalent doses of metoprolol CT.
authors.affiliation: CIBA-GEIGY Cardiovascular Clinical Research Department, Summit, NJ 07901.
authors.forename: N R
authors.initials: NR
authors.lastname: Feliciano
authors.forename: A A
authors.initials: AA
authors.lastname: Bouvet
authors.forename: E
authors.initials: E
authors.lastname: Redalieu
authors.forename: J
authors.initials: J
authors.lastname: Castellana
authors.forename: R C
authors.initials: RC
authors.lastname: Luders
authors.forename: D J
authors.initials: DJ
authors.lastname: Schwartz
authors.forename: L
authors.initials: L
authors.lastname: Shum
authors.forename: S
authors.initials: S
authors.lastname: Zak
authors.forename: J D
authors.initials: JD
authors.lastname: Arnold
authors.forename: P T
authors.initials: PT
authors.lastname: Leese
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005080:Exercise Test; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D013607:Tablets
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D008790:Metoprolol