Staessen J, Fagard R, Fiocchi R, Lijnen P, M'Buyamba-Kabangu J R, Amery A
Arch Int Pharmacodyn Ther. 1986 Jan;279(1):162-76.
After a run-in period on placebo, 26 patients with essential hypertension were prescribed single-blind tibalosine, 150 mg daily. On tibalosine their blood pressure decreased from 157/101 to 147/93 mm Hg (p less than 0.001) and their heart rate from 74 to 68 beats per minute (p less than 0.01), while plasma renin activity tended to fall from 0.81 to 0.65 ng/ml/hr (p = 0.06). Twelve patients, maintained on monotherapy with tibalosine for an average of 3.8 months, kept a diastolic pressure below 90 mm Hg. Ten patients, whose diastolic pressure on tibalosine alone remained equal to or higher than 90 mm Hg were continued on this drug for 6.6 months, but were additionally given in a double-blind and randomized way either placebo, or atenolol 100 mg, or chlorthalidone, 50 mg, daily. As compared to tibalosine plus placebo, blood pressure and heart rate decreased further on tibalosine plus atenolol from 148/97 to 140/90 mm Hg (p less than 0.05) and from 70 to 60 beats per minute (p less than 0.05), respectively. The additional blood pressure lowering effect of tibalosine plus chlorthalidone to a level of 143/96 mm Hg was not statistically significant. Eight of 10 patients' blood pressure responded better to tibalosine combined with atenolol than with chlorthalidone. Because of adverse reactions tibalosine was discontinued in 8 of the 26 patients (31%), namely in 4 who prematurely dropped out from the study and in another 4 patients, who remained adherent to the protocol. Somnolence, weary legs and dry mouth were reported more frequently (p less than 0.05) on tibalosine than on placebo.
tibalosine is an effective anti-hypertensive drug, but side effects preclude its clinical use at a daily dose of 150 mg; the combination with a beta-adrenoceptor blocking drug seems therapeutically more effective than with a thiazide.
在经过安慰剂导入期后,26例原发性高血压患者被给予单盲的替巴洛新,每日150毫克。服用替巴洛新后,他们的血压从157/101毫米汞柱降至147/93毫米汞柱(p<0.001),心率从每分钟74次降至68次(p<0.01),而血浆肾素活性有从0.81降至0.65纳克/毫升/小时的趋势(p = 0.06)。12例患者单药服用替巴洛新平均3.8个月,舒张压维持在90毫米汞柱以下。10例患者单服替巴洛新时舒张压仍等于或高于90毫米汞柱,继续服用该药6.6个月,但另外以双盲随机方式每日加用安慰剂、或阿替洛尔100毫克、或氯噻酮50毫克。与替巴洛新加安慰剂相比,替巴洛新加阿替洛尔时血压和心率进一步下降,分别从148/97毫米汞柱降至140/90毫米汞柱(p<0.05),从每分钟70次降至60次(p<0.05)。替巴洛新加氯噻酮使血压降至143/96毫米汞柱的额外降压效果无统计学意义。10例患者中有8例服用替巴洛新联合阿替洛尔时血压比联合氯噻酮时反应更好。由于不良反应,26例患者中有8例(31%)停用替巴洛新,其中4例提前退出研究,另4例仍遵守方案。与安慰剂相比,服用替巴洛新时嗜睡、腿部乏力和口干的报告更为频繁(p<0.05)。
替巴洛新是一种有效的抗高血压药物,但副作用使其无法以每日150毫克的剂量用于临床;与β肾上腺素受体阻断药联合使用在治疗上似乎比与噻嗪类药物联合更有效。