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Clinical chronopharmacology of oral sustained-release isosorbide-5-mononitrate in healthy subjects.

Abstract：

:In 10 healthy male subjects the pharmacokinetics and haemodynamic effects of sustained-release isosorbide-5-mononitrate 60 mg (IS-5-MN) were studied after oral administration at two different times in the day (08.00 h and 20.00 h). Effects on blood pressure and heart rate after 3 min standing upright were measured in relation to the individual circadian control values. The pharmacokinetic parameters (Cmax, tmax, AUC, t 1/2) did not differ after morning and after evening dosing, tmax being 5.2 h and 4.9 h, respectively. In contrast, the cardiovascular effects of IS-5-MN were clearly circadian phase-dependent. The maximum decrease in blood pressure decrease and increase in heart rate occurred significantly earlier after the evening (BPsys 2.8 h; BPdia 2.9 h; HR 3.8 h) than after the morning dose (BPsys 5.0 h; BPdia 6.0 h; HR 5.2 h). Thus, the peak haemodynamic effects coincided with the peak drug concentration after the morning dose, whereas the peak effect was in advance of the peak drug concentration after the evening dose of IS-5-MN. The data provide evidence of circadian phase-dependency in the dose-response relationship of oral IS-5-MN.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Lemmer B,Scheidel B,Blume H,Becker HJ

doi

10.1007/BF00315142

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

71-5

issue

1

eissn

0031-6970

issn

1432-1041

journal_volume

40

pub_type

杂志文章

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