Administration time-dependent effects on ambulatory blood pressure of doxazosin gits as added therapy in uncontrolled hypertensive patients

Previous studies have shown that a single nighttime dose of Doxazosin (DOX), an alpha-adrenergic antagonist with demonstrated antihypertensive effects, reduces blood pressure (BP) throughout day and night [Am J Hyp. 1994;7:844–847]. However, the potential differing effects of DOX on BP as a function of its time of administration have not yet been reported. Accordingly, we investigated the administration time-dependent effects on the 24-hour pattern of BP of the new DOX gastrointestinal therapeutic system (GITS) formulation given as added therapy in hypertensive patients. We studied 62 patients with uncontrolled grade 1–2 essential hypertension (26 men), 58.3±11.0 years of age, who were already taken an average of 2.7 drugs. Patients were randomly assigned to receive 4 mg/day DOX GITS either on awakening or before bedtime. BP was measured by ambulatory monitoring at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours at baseline and after 3 months of therapeutic intervention. Physical activity was monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. After DOX GITS on awakening, there was a small although significant reduction only in the diurnal (3.4 and 2.9 mm Hg for systolic and diastolic BP, P<0.036), but not in the nocturnal mean of BP. The antihypertensive efficacy was significantly larger (6.8 and 5.6 mm Hg reduction in the 24-hour mean of systolic and diastolic BP, P<0.001) when DOX GITS was administered before bedtime. This BP reduction was similar during daytime and nighttime hours, indicating a larger therapeutic coverage when DOX GITS was administered before bedtime. DOX GITS administered in combination therapy on awakening does not provide a full 24-hour therapeutic coverage, altering the circadian profile of BP to a more nondipping pattern (due to the BP reduction during the day and the lack of effect at night). Nighttime dosing with DOX GITS, however, significantly reduces BP both during diurnal activity and nocturnal resting hours in patients with essential hypertension. These administration time-dependent effects should be taken into consideration when prescribing DOX GITS to uncontrolled hypertensive patients. Am J Hypertens (2004) 17, 108A–109A; doi: 10.1016/j.amjhyper.2004.03.280