Ingestion-time - relative to circadian rhythms - differences in the pharmacokinetics and pharmacodynamics of hypertension medications

Introduction Hypertension guidelines do not recommend the time to administer blood pressure (BP)-lowering medications, despite multiple prospective clinical trials reporting both improved normalization of BP 24 h patterning and reduced cardiovascular disease (CVD) events when ingested at bedtime rather than upon awakening. Areas covered We review: (i) circadian rhythm-dependent influences on the pharmacokinetics (PK) and pharmacodynamics (PD) of hypertension medications; (ii) reports of ingestion-time differences in PK and PD of such therapies; and (iii) (chrono)prevention of CVD morbidity and mortality achieved by the simple and low-cost bedtime hypertension chronotherapy strategy, i.e. scheduling at bedtime >= 1 conventional BP-lowering medications to target asleep BP control of ABPM-diagnosed true arterial hypertension patients. Expert opinion Proper management of hypertension requires awareness of known ingestion-time differences in both the PK of individual BP-lowering medications and their combinations, which arise from circadian rhythms affecting absorption, distribution, metabolism, and elimination, and their PD, which result from circadian rhythms in mechanisms that regulate the 24 h BP pattern. The vast majority of the multiple published trials document substantially enhanced lowering of asleep BP, increased sleep-time relative BP decline (dipping), and markedly better reduction of CVD morbidity and mortality when hypertension medications and their combinations are ingested at bedtime rather than upon waking.