Pharmacokinetic and pharmacodynamic comparison of an osmotic release oral metoprolol tablet and the metoprolol conventional tablet.
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.
Feliciano
N R
NR
CIBA-GEIGY Cardiovascular Clinical Research Department, Summit, NJ 07901.
Bouvet
A A
AA
Redalieu
E
E
Castellana
J
J
Luders
R C
RC
Schwartz
D J
DJ
Shum
L
L
Zak
S
S
Arnold
J D
JD
Leese
P T
PT
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
D003692:Delayed-Action Preparations; D013607:Tablets; D008790:Metoprolol