Musha H, Murayama M, Motohashi F, Masuda H, Takada H, Miyake F, Sugai J
Second Department of Internal Medicine, St Marianna University, School of Medicine, Kawasaki, Japan.
Jpn Heart J. 1994 Jan;35(1):51-60. doi: 10.1536/ihj.35.51.
The aim of this study was to investigate the pharmacokinetics of propranolol in patients with hyperthyroidism, and its effect on heart rate (HR) using 24 hour-ECG monitoring. Subjects included 9 patients with hyperthyroidism (group H) and 9 euthyroid patients with hypertension selected as the control group (group C). All patients took propranolol at a dosage of 10 mg, 3 times a day for 7 days. Plasma propranolol concentrations were measured on the 7th day of its administration by the HPLC method. Twenty-four hour-ECG monitoring was recorded twice before and after treatment with propranolol. The mean reduction in the minimum HR was 10.7 +/- 3.6 (11.9 +/- 3.6%) in group H and 5.0 +/- 1.6 (9.5 +/- 3.0%) bpm in group C. That in the average HR was 12.2 +/- 3.7 (11.3 +/- 3.1%) in group H and 9.2 +/- 2.2 bpm (13.7 +/- 3.2%) in group C. That in the maximum HR was 16.9 +/- 5.2 (10.9 +/- 3.1%) in group H and 24.4 +/- 2.4 bpm (21.9 +/- 2.1%) in group C. The peak concentration of propranolol in plasma was 10.8 +/- 2.4 ng/ml in group H and 55.3 +/- 14.3 ng/ml in group C (p < 0.01). There was a linear correlation between the reduction in the hourly maximum heart rate and the peak plasma propranolol concentration in group H. Cardiovascular manifestations in hyperthyroid patients were related to sympathetic hypersensitivity and their improvement was not fully obtained by small doses of propranolol.
本研究的目的是通过24小时心电图监测，研究普萘洛尔在甲状腺功能亢进患者中的药代动力学及其对心率（HR）的影响。受试者包括9例甲状腺功能亢进患者（H组）和9例甲状腺功能正常的高血压患者作为对照组（C组）。所有患者均服用普萘洛尔，剂量为10mg，每日3次，共7天。在给药第7天，采用高效液相色谱法测定血浆普萘洛尔浓度。在普萘洛尔治疗前后，分别进行两次24小时心电图监测。H组最低心率平均降低10.7±3.6（11.9±3.6%），C组为5.0±1.6（9.5±3.0%）次/分钟。H组平均心率降低12.2±3.7（11.3±3.1%），C组为9.2±2.2次/分钟（13.7±3.2%）。H组最高心率降低16.9±5.2（10.9±3.1%），C组为24.4±2.4次/分钟（21.9±2.1%）。H组血浆普萘洛尔峰值浓度为10.8±2.4ng/ml，C组为55.3±14.3ng/ml（p<0.01）。H组每小时最高心率降低值与血浆普萘洛尔峰值浓度之间存在线性相关性。甲状腺功能亢进患者的心血管表现与交感神经超敏反应有关，小剂量普萘洛尔不能完全改善这种情况。
