Johnson J A, Akers W S, Miller S T, Applegate W B
Department of Clinical Pharmacy, University of Tennessee, Memphis 38163, USA.
Pharmacotherapy. 1995 Mar-Apr;15(2):150-7.
To evaluate whether variability in S-metoprolol kinetics and lymphocyte beta 2-receptor-mediated cyclic adenosine monophosphate (cAMP) accumulation is related to the variability in antihypertensive response to metoprolol of black men.
Prospective, unblinded study.
University-based preventive medicine clinic.
Twelve hypertensive black men.
Ambulatory blood pressure was measured over 24 hours before and after metoprolol administration. Ex vivo responsiveness of lymphocyte beta 2-receptors to isoproterenol was established for each subject before initiating metoprolol therapy. Plasma samples were collected over 12 hours at the conclusion of the study, from which metoprolol enantiomer concentrations were determined by chiral high-performance liquid chromatography, and kinetic values were calculated. The 24-hour ambulatory blood pressure responses to metoprolol were highly variable, with systolic blood pressure responses ranging from -13 to +33 mm Hg and diastolic blood pressure responses ranging from -15 to +15 mm Hg. There was a significant relationship between the metoprolol-induced change in systolic blood pressure and the maximum lymphocyte beta 2-receptor cAMP production (y = 0.47x-7.79; r2 = 0.49, p < 0.05) such that those with the highest maximum cAMP production had the greatest blood pressure increases during metoprolol therapy. There was no relationship between S-metoprolol concentration and blood pressure response. Mean oral clearance values for S- and R-metoprolol were 1320 and 2346 ml/minute, respectively.
Lymphocyte beta 2-receptor data suggest that individuals most responsive to beta-receptor stimulation may be at greatest risk of blood pressure elevation during beta 2-receptor blockade. The metoprolol enantiomer kinetic data are markedly different from previously published data and may represent racial differences in pharmacokinetics.
评估S-美托洛尔动力学及淋巴细胞β2受体介导的环磷酸腺苷（cAMP）蓄积的变异性是否与黑人男性对美托洛尔降压反应的变异性相关。
前瞻性、非盲研究。
大学预防医学诊所。
12名高血压黑人男性。
在服用美托洛尔前后24小时测量动态血压。在开始美托洛尔治疗前，为每位受试者测定淋巴细胞β2受体对异丙肾上腺素的体外反应性。在研究结束时的12小时内采集血浆样本，通过手性高效液相色谱法测定美托洛尔对映体浓度，并计算动力学值。美托洛尔的24小时动态血压反应高度可变，收缩压反应范围为-13至+33 mmHg，舒张压反应范围为-15至+15 mmHg。美托洛尔引起的收缩压变化与最大淋巴细胞β2受体cAMP产生之间存在显著关系（y = 0.47x - 7.79；r2 = 0.49，p < 0.05），因此在美托洛尔治疗期间，最大cAMP产生最高的患者血压升高幅度最大。S-美托洛尔浓度与血压反应之间无关系。S-和R-美托洛尔的平均口服清除率分别为1320和2346 ml/分钟。
淋巴细胞β2受体数据表明，对β受体刺激反应最敏感的个体在β2受体阻滞剂治疗期间血压升高的风险可能最大。美托洛尔对映体动力学数据与先前发表的数据明显不同，可能代表药代动力学的种族差异。
