Is the antihypertensive effect of captopril influenced by the dosage frequency? A study with ambulatory monitoring

When captopril was first introduced for the management of hypertension, its short plasma half-life led to its use as a thrice daily regimen. However, further experience suggests that the biological action is more prolonged than the plasma half-life might suggest. This study examined the effect of varying the frequency of administration (once, twice and three times daily) of a fixed daily dosage of 75 mg captopril on ambulatory BP in a double-blind cross-over study in 15 patients with mild to moderate hypertension. Each patient had six ambulatory BP recordings with placebo alternating with active phase. The three regimens (75 mg daily, 37.5 mg twice daily and 25 mg three times daily) reduced the daily mean BP equally and significantly compared with placebo. Three patients with very high pretreatment plasma renin values showed some loss of BP control immediately prior to the first dose in the morning in the 75 mg single dose phase (i.e. 24 hours post dose); but group analysis showed no difference in mean BP at this time point with the three treatment regimens. We conclude that in spite of its short plasma half-life, captopril can effectively control BP over the whole day with a once daily regimen.