Dell R B, Hein K, Ramakrishnan R, Puig-Antich J, Cooper T
Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York 10032.
Ther Drug Monit. 1990 Sep;12(5):450-9. doi: 10.1097/00007691-199009000-00008.
A kinetic model for imipramine (IMI) has been developed, based upon a study of 16 teenagers who received IMI 4-5 mg/kg/day for treatment of a major depressive disorder. Serial measurements of plasma concentrations of IMI, desmethylimipramine (DMI), 2-hydroxy-IMI, and 2-hydroxy-DMI were made. Mean residence times, volumes of distribution, clearances of IMI and DMI, and rate constants for formation and elimination of the hydroxy metabolites were determined from a multicompartment model fitted to the concentration-time data. Mean residence time for DMI was significantly longer than for IMI (47.1 +/- 21.2 vs. 13.4 +/- 4.8 h, p less than 0.001). A different volume of distribution for IMI and DMI was not supported by the data. Clearance of DMI was considerably slower than that of IMI (0.67 +/- 0.45 vs. 2.18 +/- 1.33 l(kg.h), p less than 0.001). A statistically significant increase in mean residence time with increasing age during adolescence was found (r = 0.57, p less than 0.05).
基于对16名青少年的研究，建立了丙咪嗪（IMI）的动力学模型，这些青少年接受4-5mg/kg/天的IMI治疗重度抑郁症。对IMI、去甲丙咪嗪（DMI）、2-羟基-IMI和2-羟基-DMI的血浆浓度进行了系列测量。根据拟合浓度-时间数据的多室模型，确定了平均驻留时间、分布容积、IMI和DMI的清除率以及羟基代谢物形成和消除的速率常数。DMI的平均驻留时间显著长于IMI（47.1±21.2对13.4±4.8小时，p<0.001）。数据不支持IMI和DMI有不同的分布容积。DMI的清除率比IMI慢得多（0.67±0.45对2.18±1.33l/(kg·h)，p<0.001）。发现青春期期间平均驻留时间随年龄增长有统计学显著增加（r=0.57，p<0.05）。
