Sg. Meeves et Gd. Park, THE USE OF CONFIDENCE-INTERVALS TO DESCRIBE THE PRECISION OF TROUGH PEAK RATIOS FOR DILTIAZEM CD IN THE TREATMENT OF HYPERTENSION/, Journal of clinical pharmacology, 34(3), 1994, pp. 231-235
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.