THE USE OF CONFIDENCE-INTERVALS TO DESCRIBE THE PRECISION OF TROUGH PEAK RATIOS FOR DILTIAZEM CD IN THE TREATMENT OF HYPERTENSION/

Once-daily diltiazem hydrochloride, CARDIZEM(R) CD (diltiazem CD) 300 mg, was evaluated for safety, efficacy, and the relationship between p eak and trough antihypertensive effects in a multicenter, placebo-cont rolled, parallel design trial. After a 4- to B-week placebo baseline p eriod, 111 patients with essential hypertension were randomized to rec eive placebo or diltiazem CD for a 4-week treatment period. Diltiazem CD 300 mg lowered supine diastolic and systolic blood pressure at trou gh significantly more than placebo (-7.5 mm Hg vs. -1.3 mm Hg, P = 0.0 001 and -6.4 mm Hg vs. 0.5 mm Hg, P = 0.0051, respectively). Supine bl ood pressure was also measured hourly from 6 to 10 hours after the dos e to assess peak effect and trough/peak ratios. Using the largest resi dual drug effect of -8.3 mm Hg at 6 hours as peak and the 24-hour resi dual drug effect of -5.9 mm Hg as trough, the trough/peak ratio was es timated to be 71%, with a lower one-sided 95% confidence limit of 50%. The precision of the trough/peak ratio is estimated by the lower conf idence limit of 50%, which establishes the trough/peak ratio as statis tically greater than or equal to 50%. No statistically significant dif ferences in supine DBP were noted between the peak effect hours, indic ating a plateau of the peak antihypertensive effect from 6 to 10 hours postdose. Diltiazem CD therapy was well tolerated, with no serious tr eatment-related adverse events reported during the trial and no patien ts discontinuing the trial due to a treatment-related adverse event. T his trial demonstrates diltiazem CD 300 mg is a safe and effective the rapy when administered once daily for the treatment of essential hyper tension.