Schaaf L J, Campbell S C, Mayersohn M B, Vagedes T, Perrier D G
College of Pharmacy, University of Arizona, Tucson.
Eur J Clin Pharmacol. 1987;33(4):355-61. doi: 10.1007/BF00637630.
The purpose of this study was to examine the influence of cigarette smoking and gender on the pharmacokinetics of metoprolol. Eighteen volunteers with no evidence of clinical disease each randomly received the following doses of metoprolol tartrate: 100 mg orally, 200 mg orally and 20 mg as a constant-rate intravenous infusion over 20 min. The only significant difference between smokers (S) and nonsmokers (NS) was that S had a larger steady-state volume of distribution (3.3 vs 2.5 l/kg). There were no differences in half-life, systemic clearance or bioavailability (f). No differences were observed between males (M) and females (FM) for any of the kinetic parameters examined. Systemic bioavailability varied markedly between subjects (range: 15 to 92%). In fifteen of the eighteen subjects, f was higher after the 200-mg dose compared to the 100-mg dose. These results suggest that metoprolol may be subject to saturable presystemic elimination and extend the previous observations of Johnsson et al. [1] who showed that f increased from 31% to 46% when doses were increased from 20 to 100 mg. However, the difference in f as the dose is increased is unlikely to be clinically significant since the mean difference is smaller than the variation in f among subjects.
本研究的目的是考察吸烟和性别对美托洛尔药代动力学的影响。18名无临床疾病证据的志愿者每人随机接受以下剂量的酒石酸美托洛尔：口服100mg、口服200mg以及在20分钟内以恒速静脉输注20mg。吸烟者（S）和非吸烟者（NS）之间唯一显著的差异是S的稳态分布容积更大（3.3 vs 2.5 l/kg）。半衰期、全身清除率或生物利用度（f）无差异。在所检测的任何动力学参数方面，男性（M）和女性（FM）之间均未观察到差异。受试者之间的全身生物利用度差异显著（范围：15%至92%）。在18名受试者中的15名中，200mg剂量后的f高于100mg剂量后的f。这些结果表明美托洛尔可能存在可饱和的首过消除，并扩展了约翰松等人[1]之前的观察结果，他们发现当剂量从20mg增加到100mg时，f从31%增加到46%。然而，随着剂量增加f的差异在临床上不太可能具有显著意义，因为平均差异小于受试者之间f的变异。
