Andreasen F, Jakobsen P, Kornerup H J, Pedersen E B, Pedersen O L, Weeke J
Br J Clin Pharmacol. 1984 Mar;17(3):265-71. doi: 10.1111/j.1365-2125.1984.tb02341.x.
Propranolol induced changes in blood plasma chemistry were followed in thirty hypertensive patients (WHO I-II) who were seen each week during 14-15 weeks. The initial 4 weeks were a drug free period and the next 2 weeks were a drug adjustment period. After that the patients were on an unchanged propranolol dose for 8 weeks (40, 80 or 160 mg four times daily). For all observed changes the correlation was studied to (1) dose, (2) free and total simultaneously determined plasma concentration and (3) free and total average plasma concentration of unchanged drug during the preceding 24 h period. Total protein and albumin did not change significantly. After 4 and 8 weeks on the final dose orosomucoid was increased significantly (by 10%) compared with the value from the end of the drug free period. Creatinine rose significantly during the initial 4-6 weeks therapy to remain at the same level during the last 4 weeks. Urate was increased at the two lowest dose levels. Total cholesterol fell significantly (5%) while triglycerides increased significantly (16%). T4 rose significantly, T3 fell and r-T3 rose significantly in a dose dependent way. Interindividually r-T3 was the only biochemical change showing a significant relationship to the propranolol plasma concentration. The relationship reached the highest level of significance to the average 24 h free concentration.
对30名高血压患者(WHO I-II级)进行了随访,观察普萘洛尔对血浆化学指标的影响。这些患者在14 - 15周内每周就诊一次。最初4周为无药期,接下来2周为药物调整期。之后患者服用固定剂量的普萘洛尔8周(每日4次,每次40、80或160毫克)。对于所有观察到的变化,研究了其与以下因素的相关性:(1)剂量;(2)同时测定的游离和总血浆浓度;(3)前24小时内未变化药物的游离和总平均血浆浓度。总蛋白和白蛋白无显著变化。在最终剂量服用4周和8周后,与无药期末的值相比,类粘蛋白显著增加(10%)。在治疗的最初4 - 6周肌酐显著上升,在最后4周保持在同一水平。尿酸在两个最低剂量水平上升。总胆固醇显著下降(5%),而甘油三酯显著上升(16%)。T4显著上升,T3下降,r - T3呈剂量依赖性显著上升。个体间r - T3是唯一与普萘洛尔血浆浓度有显著关系的生化变化。这种关系与平均24小时游离浓度的相关性达到最高显著水平。