Duration of effect of single daily dose methyldopa therapy

1 Methyldopa has a short plasma half-life, but longer duration of antihypertensive effect. A single bedtime dose of methyldopa has been recommended to improve compliance and decrease side effects. 2 This double-blind crossover study was designed to determine the duration of antihypertensive effect of methyldopa by comparing hourly supine and standing blood pressures, throughout the day during placebo, single morning dose, and single evening dose methyldopa therapy in 10 patients. The major side effects, drowsiness and dry mouth were assessed by visual analogue scale. Exercise blood pressures were measured 6, 12, 18 and 24 h after the dose. 3 The antihypertensive effect of methyldopa peaked after 6-9 h and declined thereafter with a half-life of approximately 10 h. Little antihypertensive effect remained 24-26 h after the dose. The time course of the reduction in blood pressure during exercise and of the major side effects paralleled the antihypertensive effects. 4 The results suggest that the duration of antihypertensive effect of methyldopa is long enough to permit twice daily dosing, but that single daily dosing cannot be recommended for most patients. The study illustrates the importance of knowing the time of the last methyldopa dose when assessing blood pressure measurements in patients taking the drug.