Kostis J B, Vachharajani N N, Hadjilambris O W, Kollia G D, Palmisano M, Marino M R
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, USA.
J Clin Pharmacol. 2001 Sep;41(9):935-42. doi: 10.1177/00912700122010906.
Alterations in the pharmacokinetic parameters of a number of medications have been observed in patients with heart failure. Because the angiotensin II receptor antagonist irbesartan has beneficial effects in patients with heart failure, the pharmacokinetics and pharmacodynamics of irbesartan in 10 patients with New York Heart Association (NYHA) class II or III heart failure compared with 10 control subjects matched with respect to race, age, weight, and sex were studied. In a crossover study, participants were randomized to receive open-label irbesartan 75 mg as either an oral capsule or an intravenous (i.v.) infusion in the first treatment period. After a 7- to 10-day washout period, participants were crossed over to the other treatment arm. Single-dose noncompartmental pharmacokinetic parameters, angiotensin II levels, and plasma renin activity (PRA) of irbesartan were determined for each participant. Following oral and i.v. administration, the pharmacokinetics of irbesartan in patients with heart failure was not significantly different from those of matched controls, indicating that there is little influence of potential changes in organ/tissue perfusion and gut edema on the absorption, distribution, and elimination of irbesartan. After dosing with irbesartan, mean increases in angiotensin II and PRA concentrations were higher in patients with heart failure than in the matched controls, but there was more interpatient variability in the patients with heart failure. Given the variability of the data, no definitive conclusions can be made with regard to these pharmacodynamic parameters. The results of this study indicate that the pharmacokinetics of irbesartan following oral and i.v. administration is not altered in patients with heart failure. Therefore, this indicates that no dosage adjustment is needed when prescribing irbesartan in heart failure patients.
心力衰竭患者中已观察到多种药物的药代动力学参数发生改变。由于血管紧张素II受体拮抗剂厄贝沙坦对心力衰竭患者有益，因此研究了10例纽约心脏协会（NYHA）II级或III级心力衰竭患者与10例在种族、年龄、体重和性别方面相匹配的对照受试者中厄贝沙坦的药代动力学和药效学。在一项交叉研究中，参与者在第一个治疗期被随机分配接受开放标签的75mg厄贝沙坦，剂型为口服胶囊或静脉输注。经过7至10天的洗脱期后，参与者交叉至另一个治疗组。测定了每位参与者厄贝沙坦的单剂量非房室药代动力学参数、血管紧张素II水平和血浆肾素活性（PRA）。口服和静脉给药后，心力衰竭患者中厄贝沙坦的药代动力学与匹配的对照受试者相比无显著差异，表明器官/组织灌注和肠道水肿的潜在变化对厄贝沙坦的吸收、分布和消除影响很小。服用厄贝沙坦后，心力衰竭患者中血管紧张素II和PRA浓度的平均升高高于匹配的对照受试者，但心力衰竭患者之间的个体差异更大。鉴于数据的变异性，关于这些药效学参数无法得出明确结论。本研究结果表明，口服和静脉给药后，心力衰竭患者中厄贝沙坦的药代动力学未发生改变。因此，这表明在为心力衰竭患者开具厄贝沙坦处方时无需调整剂量。
