Blum R A, Olson S C, Kohli R K, Horvath A M, Sedman A J, Posvar E L
Clinical Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo, NY 14209.
J Clin Pharmacol. 1990 Oct;30(10):938-42. doi: 10.1002/j.1552-4604.1990.tb03574.x.
The pharmacokinetics of quinapril and its active metabolite, quinaprilat, were evaluated in 12 patients with end-stage renal disease (ESRD) on chronic hemodialysis. Each subject received a single 20-mg oral dose of quinapril 4 hours before a 4-hour hemodialysis treatment. Serial dialysate and blood samples were obtained over 4 and 96 hours, respectively. Samples were analyzed for quinapril and quinaprilat concentrations by gas chromatography. Mean tmax and Cmax values for quinapril were 1.2 hours and 129 ng/mL, respectively. Only one patient had detectable quinapril dialysate concentrations which accounted for 2.8% of the quinapril dose. Mean apparent plasma clearance for quinapril was 1275 mL/min with a mean half-life of 1.7 hours. Quinapril was extensively de-esterified to its diacid metabolite, quinaprilat. Mean tmax and Cmax for quinaprilat were 4.5 hours and 671 ng/mL, respectively. Mean apparent plasma clearance for quinaprilat was 24.0 mL/min with a mean half-life of 17.5 hours. As with quinapril, quinaprilat was not readily dialyzable. Only 5.4% of the administered quinapril dose was recovered as quinaprilat during a single hemodialysis treatment. In view of these results, supplemental quinapril doses need not be routinely given to patients following hemodialysis. Overall, quinapril and quinaprilat pharmacokinetics in patients with ESRD on chronic hemodialysis were not markedly different from those previously observed in patients with moderate to severe renal dysfunction (CLcr less than 29 mL/min) not yet requiring hemodialysis (RDND).
在12例接受慢性血液透析的终末期肾病（ESRD）患者中评估了喹那普利及其活性代谢产物喹那普利拉的药代动力学。在4小时血液透析治疗前4小时，每位受试者口服单次20 mg剂量的喹那普利。分别在4小时和96小时内采集系列透析液和血样。通过气相色谱法分析样品中的喹那普利和喹那普利拉浓度。喹那普利的平均达峰时间（tmax）和峰浓度（Cmax）分别为1.2小时和129 ng/mL。仅1例患者的透析液中可检测到喹那普利浓度，占喹那普利剂量的2.8%。喹那普利的平均表观血浆清除率为1275 mL/min，平均半衰期为1.7小时。喹那普利广泛脱酯形成其二酸代谢产物喹那普利拉。喹那普利拉的平均tmax和Cmax分别为4.5小时和671 ng/mL。喹那普利拉的平均表观血浆清除率为24.0 mL/min，平均半衰期为17.5小时。与喹那普利一样，喹那普利拉不易被透析清除。在单次血液透析治疗期间，仅5.4%的给药喹那普利剂量以喹那普利拉的形式被回收。鉴于这些结果，血液透析后的患者无需常规给予喹那普利补充剂量。总体而言，慢性血液透析的ESRD患者中喹那普利和喹那普利拉的药代动力学与之前在尚未需要血液透析的中度至重度肾功能不全（肌酐清除率低于29 mL/min）患者（RDND）中观察到的情况无明显差异。
