Bianchetti G, Graziani G, Brancaccio D, Morganti A, Leonetti G, Manfrin M, Sega R, Gomeni R, Ponticelli C, Morselli P L
Clin Pharmacokinet. 1976;1(5):373-84. doi: 10.2165/00003088-197601050-00004.
Propranolol blood and plasma levels were measured after a single oral dose of 40 mg in patients with chronic renal failure, in patients undergoing regular dialysis treatment, and in healthy volunteers. Peak levels were observed in all cases within 1.5 to 3 hours. However, peak blood and plasma concentrations of propranolol in the chronic renal failure group were 2- to 3-fold higher (161 +/- 41 ng/ml) than those observed in the dialysis patients (47 +/- 9 ng/ml) and in the healthy volunteers (26 +/- 1 ng/ml). The apparent plasma clearance was also significantly reduced in the patients with chronic renal failure. The data suggest a reduced hepatic extraction in chronic renal failure patients. A significant increase in the fraction of the dose available to the systemic circulation was also found, together with a modification of apparent plasma half-life and volume of distribution in regular dialysis patients during the dialysis day as compared with the after-dialysis day. No extraction of propranolol by the dialyzer was noticed. Marked fluctuations in propranolol blood concentrations were also observed in patients on regular dialysis following continuous propranolol treatment. The suppressive effect of propranolol on plasma renin activity did not fully correlate with the hypotensive effect of the drug. On the basis of the reported data, propranolol should be used with great caution and at low doses in chronic renal failure.
在慢性肾衰竭患者、接受定期透析治疗的患者以及健康志愿者中,单次口服40毫克普萘洛尔后测量了其血液和血浆水平。在所有情况下,均在1.5至3小时内观察到峰值水平。然而,慢性肾衰竭组中普萘洛尔的血液和血浆峰值浓度比透析患者(47±9纳克/毫升)和健康志愿者(26±1纳克/毫升)中观察到的浓度高2至3倍(161±41纳克/毫升)。慢性肾衰竭患者的表观血浆清除率也显著降低。数据表明慢性肾衰竭患者肝脏提取率降低。还发现全身循环中可用剂量的分数显著增加,并且与透析后一天相比,定期透析患者在透析日的表观血浆半衰期和分布容积有所改变。未发现透析器对普萘洛尔有提取作用。在持续服用普萘洛尔治疗的定期透析患者中,也观察到普萘洛尔血液浓度有明显波动。普萘洛尔对血浆肾素活性的抑制作用与该药物的降压作用并不完全相关。根据报告的数据,在慢性肾衰竭患者中应极其谨慎地使用普萘洛尔并采用低剂量。