单次及重复剂量奥卡西平对非洛地平药代动力学特征的影响。

Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine.

作者信息

Zaccara G, Gangemi P F, Bendoni L, Menge G P, Schwabe S, Monza G C

机构信息

Department of Neurological and Psychiatric Sciences, University of Florence, Italy.

出版信息

Ther Drug Monit. 1993 Feb;15(1):39-42. doi: 10.1097/00007691-199302000-00007.

DOI:10.1097/00007691-199302000-00007

PMID:8451779

Abstract

Eight healthy male volunteers (age 25-41 years) entered an open-label, within-subject study. They were treated for 13 consecutive days with felodipine (FEL) extended-release tablets, 10 mg daily. On day 6, oxcarbazepine (OXC) 600 mg was given in the morning, and from day 7 to 13, the daily dose was increased to 450 mg b.i.d. Blood samples for measurement of FEL and its pyridine metabolite (determined by gas-chromatography) were drawn just before dosing and at 2, 4, 6, 8, 10, 12, and 24 h after dosing on days 5, 6, and 13. Steady-state pharmacokinetic parameters of FEL and its pyridine metabolite were not influenced by the single dose of OXC. Repeated coadministration of OXC significantly reduced the area under the concentration-time curve (AUC0-24) of FEL by 28% and the FEL maximum plasma concentration (Cmax) by 34%. This reduction in FEL bioavailability is much smaller than that observed after co-administration of carbamazepine (CBZ) (i.e., 94%).

摘要

八名健康男性志愿者（年龄25 - 41岁）参与了一项开放标签的自身对照研究。他们连续13天每日服用10毫克非洛地平（FEL）缓释片。在第6天上午给予600毫克奥卡西平（OXC），从第7天至第13天，每日剂量增加至450毫克，每日两次。在第5、6和13天给药前以及给药后2、4、6、8、10、12和24小时采集血样，用于测定FEL及其吡啶代谢物（通过气相色谱法测定）。单次服用OXC未影响FEL及其吡啶代谢物的稳态药代动力学参数。重复联合服用OXC可使FEL的浓度 - 时间曲线下面积（AUC0 - 24）显著降低28%，FEL的最大血浆浓度（Cmax）降低34%。FEL生物利用度的这种降低远小于卡马西平（CBZ）联合给药后观察到的降低幅度（即94%）。