The cardiovascular system and daily variation in response to antihypertensive and antianginal drugs: recent advances.

This review contains recent data on the pharmacokinetics and the hemodynamic effects on heart rate and blood pressure of three different groups of drugs (beta-blockers: propranolol; oral nitrates: isosorbide-dinitrate (ISDN), isosorbide-5-mononitrate (IS-5-MN); calcium channel blockers: nifedipine) which were investigated in healthy volunteers or in hypertensive patients after drug application at different times of the day. In the case of IS-5-MN and nifedipine two different galenic formulations were studied. The results clearly demonstrate chronopharmacokinetics for propranolol, ISDN, and the immediate-release formulations of IS-5-MN and nifedipine, whereas no pharmacokinetic daily variations were observed with the sustained-release formulations. However, all drugs exhibited daily variations in their hemodynamic effects. These data greatly support the view that pharmacokinetics and drug effects should be studied simultaneously when chronopharmacologic studies are performed.