Feliciano N R, Bouvet A A, Redalieu E, Castellana J, Luders R C, Schwartz D J, Shum L, Zak S, Arnold J D, Leese P T
CIBA-GEIGY Cardiovascular Clinical Research Department, Summit, NJ 07901.
Am Heart J. 1990 Aug;120(2):483-9. doi: 10.1016/0002-8703(90)90109-b.
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.
进行了四项双盲拉丁方研究，以比较美托洛尔渗透泵片（口服渗透型）和美托洛尔常规片剂（CT）的药代动力学和药效学生物利用度。美托洛尔渗透泵片（7/95毫克或14/190毫克）每天给药一次，剂量相当于美托洛尔CT 100毫克，分别每日给药1次、2次、3次和4次。在所有四项研究中，与美托洛尔CT相比，美托洛尔渗透泵片后的血浆峰浓度较低，达峰时间较长，表明美托洛尔渗透泵片具有控释特性。通过运动心率降低来衡量的β-肾上腺素能阻滞作用，美托洛尔渗透泵片后比美托洛尔CT后更低，但美托洛尔渗透泵片提供了更平稳、更持久的β-阻滞作用。美托洛尔渗透泵片在稳态下的所有四个剂量产生的相对药效学生物利用度为等效剂量美托洛尔CT产生的生物利用度的87%至104%。
