Skoutakis V A, Acchiardo S A, Carter C A, Ingebretsen C G, Klausner M A, Lee D K, Kraml M
Department of Clinical Pharmacy, University of Tennessee, Memphis.
J Clin Pharmacol. 1988 May;28(5):467-76. doi: 10.1002/j.1552-4604.1988.tb05762.x.
The efficacy, safety, and pharmacokinetic parameters of a 30-mg oral dose of cetamolol hydrochloride (Betacor), a new synthetic cardioselective beta-adrenoceptor antagonist, with intrinsic sympathomimetic activity, were evaluated by studying 32 hypertensive patients with normal renal function or different degrees of renal impairment. After administration of cetamolol, serial blood and urine sample collections, as well as vital sign determinations for the next 48 hours, were performed in all patients (with the exception of urine collection, which was not possible in hemodialysis patients). Results indicate that cetamolol's pharmacokinetic parameters are significantly changed in patients who have moderate or severe renal impairment. Specifically, as the severity of renal impairment increased, the maximum serum concentration (Cmax) and the area under the serum concentration-time curve (AUC) increased, whereas the renal clearance (CLR), urinary excretion, and total body clearance (CL) decreased. Additionally, significant direct or inverse correlations for AUC, CL, CLR, and urinary excretion with creatinine clearance (CLCR) were demonstrated. In the subjects with mild renal impairment, the trends toward changes in the cetamolol pharmacokinetic parameters were evident, though small and not statistically significant. Although anuric, patients on hemodialysis still retained the ability metabolically to clear cetamolol at a rate of about one-third of that found in normal subjects. Reductions in blood pressure and heart rate also were found to be greater and more prolonged as the severity of renal impairment increased. There were no adverse drug or toxic effects noted in any of the study patients. Based on these findings, dosing recommendations are suggested for patients who have compromised renal function because of the effects of renal function on the pharmacokinetics of cetamolol.
通过对32例肾功能正常或有不同程度肾功能损害的高血压患者进行研究，评估了一种新型合成的具有内在拟交感活性的心脏选择性β-肾上腺素能受体拮抗剂——30毫克口服剂量的盐酸塞他洛尔（倍他洛尔）的疗效、安全性和药代动力学参数。在所有患者中（除血液透析患者无法进行尿液收集外），给予塞他洛尔后，在接下来的48小时内进行了系列血液和尿液样本采集以及生命体征测定。结果表明，中度或重度肾功能损害患者中，塞他洛尔的药代动力学参数有显著变化。具体而言，随着肾功能损害严重程度的增加，血清最大浓度（Cmax）和血清浓度-时间曲线下面积（AUC）升高，而肾清除率（CLR）、尿排泄率和全身清除率（CL）降低。此外，还证明了AUC、CL、CLR和尿排泄与肌酐清除率（CLCR）之间存在显著的直接或反向相关性。在轻度肾功能损害的受试者中，塞他洛尔药代动力学参数的变化趋势明显，尽管变化较小且无统计学意义。虽然无尿，但血液透析患者仍保留以约正常受试者三分之一的速率代谢清除塞他洛尔的能力。还发现随着肾功能损害严重程度的增加，血压和心率的降低幅度更大且持续时间更长。在任何研究患者中均未观察到药物不良反应或毒性作用。基于这些发现，针对因肾功能对塞他洛尔药代动力学的影响而导致肾功能受损的患者，提出了给药建议。
