Yoshida A, Takeda A, Fukuda M, Toda S, Morozumi K
Division of Nephrology, Nagoya Daini Red Cross Hospital.
Nihon Jinzo Gakkai Shi. 2000 May;42(4):333-7.
Trandolapril is a newly developed angiotensin converting enzyme inhibitor (ACEI) whose characteristic is that it undergoes hepatic excretion. ACEI appears to have a specific reno-protective and antiproteinuric role in patients with chronic glomerulonephritis(CGN). Although renally excreted ACEI tend to accumulate and cause side-effects in patients with renal dysfunction, the pharmacokinetics of trandolapril were not affected by renal dysfunction. We compared the effect of other renally excreted ACEI with those of trandolapril on serum creatinine (s-Cr), creatinine clearance(Ccr), proteinuria and total protein(TP) in CGN patients who switched from another ACEI to trandolapril. Twelve hypertensive patients with chronic renal failure(nine males and three females, ranging from 30 to 72 years of age) who were treated by other renally excreted ACEIs for long periods(2 to 8 years) with some effects on proteinuria and renal function, were enrolled in the present study. After ACEI therapy, s-Cr had decreased(2.09 to 1.80 mg/dl, p < 0.01) as well as proteinuria(1.65 to 0.71 g/day, p < 0.01). A single daily oral dose of 1 mg of trandolapril was administered to these patients regardless of their blood pressure status and renal functions. After change to trandolapril therapy, s-Cr(2.25 to 2.06 mg/dl, p < 0.01) and urinary protein(1.82 to 1.34 g/day, p < 0.05) significantly decreased. On the contrary, both Ccr and TP significantly increased at the level of 39.4 to 44.4 ml/min(p < 0.05) and 6.80 to 7.02 g/dl (p < 0.01), respectively. No apparent side effects, such as hyperkalemia, hyponatremia, anemia or worsening of the existing renal dysfunction except for coughing, were observed in these patients. Furthermore, none of the 12 patients treated with trandolapril required discontinuation of the compound. In conclusion, it was shown from this study that trandolapril is effective for the treatment of hypertensive patients with renal insufficiency irrespective of the original diseases. Thus, it can be envisaged that trandolapril is one of the most appropriate agents compared to other renally excreted ACEI for these patients with renal insufficiency. We recommend the change from other ACEIs to trandolapril, when renal dysfunction might be due to ACEI accumulation.
群多普利是一种新开发的血管紧张素转换酶抑制剂(ACEI),其特点是经肝脏排泄。ACEI似乎对慢性肾小球肾炎(CGN)患者具有特定的肾脏保护和抗蛋白尿作用。尽管经肾脏排泄的ACEI在肾功能不全患者中容易蓄积并引起副作用,但群多普利的药代动力学不受肾功能不全的影响。我们比较了其他经肾脏排泄的ACEI与群多普利对从另一种ACEI转换为群多普利的CGN患者血清肌酐(s-Cr)、肌酐清除率(Ccr)、蛋白尿和总蛋白(TP)的影响。12例慢性肾衰竭高血压患者(9例男性,3例女性,年龄30至72岁),长期(2至8年)接受其他经肾脏排泄的ACEI治疗,对蛋白尿和肾功能有一定影响,纳入本研究。ACEI治疗后,s-Cr下降(从2.09降至1.80mg/dl,p<0.01),蛋白尿也下降(从1.65降至0.71g/天,p<0.01)。无论患者血压状况和肾功能如何,均给予每日单次口服1mg群多普利。改为群多普利治疗后,s-Cr(从2.25降至2.06mg/dl,p<0.01)和尿蛋白(从1.82降至1.34g/天,p<0.05)显著下降。相反,Ccr和TP分别显著升高至39.4至44.4ml/min(p<0.05)和6.80至7.02g/dl(p<0.01)。这些患者未观察到明显的副作用,如高钾血症、低钠血症、贫血或除咳嗽外现有肾功能不全的恶化。此外,接受群多普利治疗的12例患者中无一例需要停用该药物。总之,本研究表明群多普利对肾功能不全的高血压患者有效,无论其原发病如何。因此,可以设想,与其他经肾脏排泄的ACEI相比,群多普利是这些肾功能不全患者最合适的药物之一。当肾功能不全可能是由于ACEI蓄积所致时,我们建议从其他ACEI改为群多普利。