Ingestion-time differences in the pharmacodynamics of hypertension medications: Systematic review of human chronopharmacology trials

Pharmacokinetics of hypertension medications is significantly affected by circadian rhythms that influence absorption, distribution, metabolism and elimination. Furthermore, their pharmacodynamics ingestion-time differences in kinetics comprising the biological mechanism 24 h blood pressure (BP) pattern. However, guidelines do not recommend time to treat patients with medications. We conducted a systematic review published evidence regarding combinations on ambulatory BP-lowering, safety, markers target organ pathology. Some 153 trials between 1976 2020, totaling 23,869 hypertensive individuals, evaluated 37 different single 14 dual-fixed combination therapies. The vast (83.7%) majority report clinically statistically significant benefits – including enhanced reduction asleep BP without inducing sleep-time hypotension, reduced prevalence higher cardiovascular disease risk non-dipping profile, decreased incidence adverse effects, improved renal function, cardiac pathology when are ingested at-bedtime/evening rather than upon-waking/morning. Non-substantiated treatment-time difference effects small proportion (16.3%) likely explained deficiencies study design conduct. Systematic comprehensive literature past 45 years reveals no reported better benefit still conventional, yet unjustified medical evidence, upon-waking/morning treatment schedule.