Blumer Jeffrey L, Daniels Stephen R, Dreyer William J, Batisky Donald, Walson Philip D, Roman Doina, Ouellet Daniele
University Hospitals of Cleveland, Cleveland, Ohio, USA.
J Clin Pharmacol. 2003 Feb;43(2):128-32. doi: 10.1177/0091270002239820.
Quinapril pharmacokinetics were studied in infants and children using a novel study design that allowed substitution of quinapril for one dose of the current chronic angiotensin-converting enzyme (ACE) inhibitor treatment. A total of 24 patients ranging in age from 2.5 to 82 months who were receiving an ACE inhibitor held their usual treatment on the study day and received a 0.2-mg/kg dose of quinapril syrup. Blood samples were collected through 24 hours postdose, and plasma was analyzed for quinapril and its active metabolite, quinaprilat. Quinapril was rapidly converted to quinaprilat. Quinaprilat concentrations generally peaked 1 to 2 hours postdose and declined with a mean half-life of 2.30 hours. Dosing on a mg/kg basis resulted in quinaprilat AUC and Cmax values that were generally comparable across the age range of patients in this study. The overall mean AUC0-infinity was 993 ng.h/mL (range: 533-1523), and mean Cmax was 260 ng/mL (range: 70.0-445.5). Quinaprilat CL/F correlated well with body size (body surface area or weight) and creatinine clearance (mL/min). Pharmacokinetic results after a 0.2-mg/kg dose in infants and children are comparable to those observed following a 10-mg dose in adults.
采用一种新颖的研究设计，在婴儿和儿童中研究了喹那普利的药代动力学，该设计允许用喹那普利替代一剂当前正在使用的慢性血管紧张素转换酶（ACE）抑制剂治疗。共有24例年龄在2.5至82个月之间且正在接受ACE抑制剂治疗的患者在研究日维持其常规治疗，并接受0.2mg/kg剂量的喹那普利糖浆。给药后24小时内采集血样，分析血浆中的喹那普利及其活性代谢物喹那普利拉。喹那普利迅速转化为喹那普利拉。喹那普利拉浓度一般在给药后1至2小时达到峰值，并以平均半衰期2.30小时下降。以mg/kg为基础给药导致喹那普利拉的AUC和Cmax值在本研究患者的年龄范围内总体上具有可比性。总体平均AUC0-∞为993ng·h/mL（范围：533 - 1523），平均Cmax为260ng/mL（范围：70.0 - 445.5）。喹那普利拉的CL/F与体型（体表面积或体重）和肌酐清除率（mL/min）密切相关。婴儿和儿童服用0.2mg/kg剂量后的药代动力学结果与成人服用10mg剂量后观察到的结果相当。
