Evaluation of the effect of time dependent dosing on pharmacokinetic and pharmacodynamics of amlodipine in normotensive and hypertensive human subjects

Abstract

In clinical practice, circadian rhythms play a prominent role in pharmacokinetics and cell responses to therapy, hence necessitating in designing a defined protocol for drug administration. Clinical evidence for chronopharmacological behavior of cardiovascular active drugs in human subjects has been limited for amlodipine. Hence, the present study was undertaken to study the chronopharmacokinetic and chronopharmacodynamic phenomena of amlodipine and evaluate the effect of time of dosage in hypertensive subjects. Single oral dose of amlodipine was administered to the hypertensive/normotensive subjects either morning or evening to assess the pharmacokinetic profile after morning dosing or evening dosing, respectively. PK parameters obtained revealed that Tmax was shorter and Cmax was greater after evening dosing than the morning dosing in both hypertensive and normotensive subjects. These observations were comparable with the hypothesis that amlodipine is absorbed rapidly when it is given during the night time. Also, the changes in systolicBP, DiastolicBP, and heart rate in comparison to the respective circadian baseline values were markedly different depending on the time and dosing. SBP and HR were significantly reduced after evening dosing with slight difference in measurement of DBP in hypertensive patients. Hence, it can be concluded that prescription of antihypertensive medications containing amlodipine, to be administered at night offers highly efficacious means to control BP without the need to increase either the dose or number of medications. The current treatment strategy method involves delivery of medications, so that they are synchronized in time to biological need that varies according to the chronobiology of the targeted tissues.

Keywords

• amlodipine
• chronopharmacodynamic
• chronopharmacokinetics
• hypertensive
• normotensive