Li Kun-Yan, Li Xin, Cheng Ze-Neng, Zhang Bi-Kui, Peng Wen-Xing, Li Huan-De
Clinical Pharmaceutical Research Institute, Hunan Provincial Tumor Hospital of China, Changsha, China.
Eur J Clin Pharmacol. 2005 Jan;60(11):791-5. doi: 10.1007/s00228-004-0853-x. Epub 2004 Dec 14.
To study the effect of erythromycin on metabolism of quetiapine in Chinese suffering from schizophrenia.
Nineteen patients received multiple doses of quetiapine (200 mg, twice daily) with or without co-administered erythromycin (500 mg, three times daily). Blood samples were collected at specified time intervals for determination of plasma concentrations of quetiapine and some of its metabolites.
With erythromycin co-administration: for quetiapine, maximal plasma concentration (Cmax), area under concentration-time curve of 0-infinity h (AUC0-infinity) and terminal-phase elimination half-life time (t1/2) increased 68, 129 and 92%, respectively, and clearance (CL) and terminal elimination rate constant (Ke) decreased 52% and 55%, respectively; for quetiapine sulfoxide (QTP-SF), Cmax, AUC0-infinity and AUC ratio decreased 64, 23, and 70%, respectively, and t1/2 increased 211%; for 7-hydroxy-quetiapine (QTP-H), Ke and AUC ratio decreased 61% and 45%, respectively, and t1/2 increased 203%; for 7-hydroxy-N-desalkyl-quetiapine (QTP-ND), Cmax, AUC0-infinity and AUC ratio decreased 36, 40 and 71%, respectively.
Erythromycin has a noticeable effect on the metabolism of quetiapine. When quetiapine is co-administered with CYP3A inhibitors such as erythromycin, the dosing regimen should be modified according to quetiapine TDM.
研究红霉素对中国精神分裂症患者喹硫平代谢的影响。
19例患者接受多剂量喹硫平（200mg，每日两次），同时或不同时联合使用红霉素（500mg，每日三次）。在特定时间间隔采集血样，以测定喹硫平及其一些代谢产物的血浆浓度。
联合使用红霉素时：对于喹硫平，血浆最大浓度（Cmax）、0至无穷大小时的浓度-时间曲线下面积（AUC0-无穷大）和终末相消除半衰期（t1/2）分别增加68%、129%和92%，清除率（CL）和终末消除速率常数（Ke）分别降低52%和55%；对于喹硫平亚砜（QTP-SF），Cmax、AUC0-无穷大及AUC比值分别降低64%、23%和70%，t1/2增加211%；对于7-羟基喹硫平（QTP-H），Ke和AUC比值分别降低61%和45%，t1/2增加203%；对于7-羟基-N-去烷基喹硫平（QTP-ND），Cmax、AUC0-无穷大及AUC比值分别降低36%、40%和71%。
红霉素对喹硫平的代谢有显著影响。当喹硫平与红霉素等CYP3A抑制剂合用时，应根据喹硫平的血药浓度监测调整给药方案。
