Siegmund W, Kairies M, Franke G, Donner I, Biebler K E
Int J Clin Pharmacol Ther Toxicol. 1987 Mar;25(3):148-51.
In 9 hypertensive patients stage II we studied whether dihydralazine, which is known to increase the renal blood flow, influences the elimination of furosemide (40 mg i.v.) when given additionally over a period of 2 weeks (75 mg daily). The results were compared with data from 9 healthy volunteers. The most important alterations in hypertonics were significantly increased half-lives (28.0 +/- 3.7 and 35.1 +/- 5.7 min), distribution coefficients (0.105 +/- 0.017 and 0.132 +/- 0.028 ml/g) and unchanged plasma clearances (2.62 +/- 0.33 and 2.59 +/- 0.27 ml min-1 X kg-1). Pretreatment with dihydralazine resulted in normalization of distribution coefficients (0.134 +/- 0.027 and 0.102 +/- 0.020 ml/g), decrease in plasma clearance (2.55 +/- 0.29 and 2.08 +/- 0.23 ml min-1 X kg-1) without alterations in half-lives (36.3 +/- 6.0 and 34.2 +/- 7.0 min). The authors conclude that the effects after dihydralazine co-medication are only distribution mediated.
在9例II期高血压患者中,我们研究了已知可增加肾血流量的双肼屈嗪在额外给药2周(每日75毫克)时是否会影响静脉注射40毫克呋塞米的消除。将结果与9名健康志愿者的数据进行比较。高血压患者最重要的变化是半衰期显著延长(分别为28.0±3.7分钟和35.1±5.7分钟)、分布系数增加(分别为0.105±0.017毫升/克和0.132±0.028毫升/克)以及血浆清除率不变(分别为2.62±0.33毫升·分钟⁻¹·千克⁻¹和2.59±0.27毫升·分钟⁻¹·千克⁻¹)。用双肼屈嗪预处理可使分布系数正常化(分别为0.134±0.027毫升/克和0.102±0.020毫升/克),血浆清除率降低(分别为2.55±0.29毫升·分钟⁻¹·千克⁻¹和2.08±0.23毫升·分钟⁻¹·千克⁻¹),而半衰期无变化(分别为36.3±6.0分钟和34.2±7.0分钟)。作者得出结论,联合使用双肼屈嗪后的效应仅由分布介导。