MK-571对映体的剂量依赖性动力学以及白三烯D4受体拮抗剂。

Dose-dependent kinetics of the enantiomers of MK-571, and LTD4-receptor antagonist.

作者信息

Depré M, Margolskee D J, Van Hecken A, Hsieh J S, Buntinx A, De Schepper P J, Rogers J D

机构信息

Department of Pharmacology, School of Medicine, University of Leuven, Belgium.

出版信息

Eur J Clin Pharmacol. 1992;43(4):431-3. doi: 10.1007/BF02220622.

DOI:10.1007/BF02220622

PMID:1451726

Abstract

The disposition of the enantiomers of MK-571 (MK-0679 and L-668,018) following single i.v. doses of MK-571 (L-660,711) was studied in a three way cross-over study in 12 healthy male volunteers. Each volunteer received 75 mg, 300 mg and 600 mg i.v. doses of MK-571 at weekly intervals. The disposition of both enantiomers appeared dose-dependent, since the AUC increased disproportionately faster than the dose. The dose dependency was much more pronounced for L-668,018: its AUC increased 6-fold from the 75 to the 300 mg dose, 16-fold from 75 to 600 mg and 2.7 fold from 300 to 600 mg. For MK-0679, the corresponding increases in AUC were 4.8-, 11-, and 2.3 fold. Regardless of dose, the elimination of L-668,018 was more rapid than that of MK-0679. The disposition of MK-0679 needs to be investigated independently to detect any potential influence of L-668,018 on its disposition.

摘要

在一项针对12名健康男性志愿者的三交叉研究中，研究了单次静脉注射MK-571（L-660,711）后MK-571对映体（MK-0679和L-668,018）的处置情况。每位志愿者每周间隔静脉注射75 mg、300 mg和600 mg的MK-571。两种对映体的处置情况均呈现剂量依赖性，因为曲线下面积（AUC）的增加比例远高于剂量增加比例。L-668,018的剂量依赖性更为明显：其AUC从75 mg剂量增加到300 mg剂量时增加了6倍，从75 mg增加到600 mg时增加了16倍，从300 mg增加到600 mg时增加了2.7倍。对于MK-0679，AUC的相应增加倍数分别为4.8倍、11倍和2.3倍。无论剂量如何，L-668,018的消除速度都比MK-0679快。需要独立研究MK-0679的处置情况，以检测L-668,018对其处置的任何潜在影响。