Rongen G A, Lenders J W, Kleinbloesem C H, Weber C, Welker H, Fahrner E, Pozenel H, Woittiez A J, Haug G, Buchmann M S
Department of Medicine, University Hospital Nijmegen, The Netherlands.
Clin Pharmacol Ther. 1993 Nov;54(5):567-77. doi: 10.1038/clpt.1993.189.
The efficacy of multiple oral administration of the renin inhibitor Ro 42-5892 (S)-alpha--methyl]hydrocinnamamido]-N-[1S , 2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]-imi dazole-4- propionamide] was studied. Forty-nine patients with moderate essential hypertension were randomly assigned to three groups that entered an 8-day double-blind oral treatment period: daily administration of placebo (group A), 300 mg Ro 42-5892 (group B), or 600 mg Ro 42-5892 (group C). Four hours after the last oral drug intake, placebo was administered intravenously to subjects in group A and 100 mg Ro 42-5892 was administered intravenously to subjects in groups B and C. Sitting systolic and diastolic blood pressures were measured on days 1 and 8 with a blood pressure device. On day 1, systolic blood pressure maximally decreased by 13.3 +/- 9.3, 20.2 +/- 11.2, and 24.1 +/- 11.3 mm Hg in groups A, B, and C, respectively (mean +/- SD; p < 0.01 for group A versus group C). Diastolic blood pressure maximally decreased 9.4 +/- 5.7, 13.9 +/- 8.7, and 11.8 +/- 5.7 mm Hg (difference not significant). On day 8, systolic blood pressure maximally decreased 19.5 +/- 16.5, 26.5 +/- 17.4, and 30.5 +/- 18.4 mm Hg and diastolic blood pressure maximally decreased 14.8 +/- 5.0, 16.2 +/- 9.0, and 17.9 +/- 12.7 mm Hg (difference not significant) compared with pretreatment values. Intravenous drug administration did not further reduce blood pressure, suggesting that the mode of action and not the low bioavailability was the limiting factor for the low efficacy.
对肾素抑制剂Ro 42 - 5892 [（S）-α-（叔丁基磺酰基）-甲基]氢化肉桂酰胺-N- [（1S，2R，3S）-1-（环己基甲基）-3-环丙基-2,3-二羟基丙基]-咪唑-4-丙酰胺]多次口服给药的疗效进行了研究。49例中度原发性高血压患者被随机分为三组，进入为期8天的双盲口服治疗期：每日服用安慰剂（A组）、300 mg Ro 42 - 5892（B组）或600 mg Ro 42 - 5892（C组）。在最后一次口服药物摄入4小时后，A组受试者静脉注射安慰剂，B组和C组受试者静脉注射100 mg Ro 42 - 5892。在第1天和第8天使用血压计测量坐位收缩压和舒张压。在第1天，A组、B组和C组的收缩压最大降幅分别为13.3±9.3、20.2±11.2和24.1±11.3 mmHg（均值±标准差；A组与C组相比，p<0.01）。舒张压最大降幅分别为9.4±5.7、13.9±8.7和11.8±5.7 mmHg（差异不显著）。在第8天，与治疗前值相比，收缩压最大降幅为19.5±16.5、26.5±17.4和30.5±18.4 mmHg，舒张压最大降幅为14.8±5.0、16.2±9.0和17.9±12.7 mmHg（差异不显著）。静脉给药并未进一步降低血压，这表明作用方式而非低生物利用度是疗效低的限制因素。
