"A Comparative Pharmacokinetic and Pharmacodynamic Study of Morning versus Evening Administration of Valsartan in Healthy Adults"

Abstract

Understanding the factors that affect the therapeutic effect of drugs is essential to optimize dosing regimens. One source of variation is introduced by the 24 h rhythms in physiology, which are generated by an endogenous clock mechanism that is entrained to light–dark cycle. These rhythms are known to affect the pharmacokinetics, and the pharmacodynamics of drugs. Many physiological processes in the human body are subject to 24 h fluctuations such as gastric emptying time, kidney function, and hepatic en-zyme activity. The complex interplay between these rhythms may result in substantial variation in the pharmacokinetic parameters of a drug over the day and the night. Valsartan is an ARB that has been widely used in treatment of hyper-tension, heart failure, and myocardial infarction. Dose‑dependent anti-hypertensive efficacy has been demonstrated for valsartan at doses up to 320 mg, with 160 mg as the recommended starting dose. Valsartan (160 mg) used as once daily regimen without any specifica-tion of time of administration. Several studies have documented variability in pharmacodynamics of valsartan, according to time of administration, influ-encing its therapeutic and adverse effects. This variability could be explained partly by time dependent variation in PK of valsartan. Circadian time-