Antihypertensive monotherapy with tablet (Prompt-release) diltiazem: Multicenter controlled trials

Abstract

The tablet formulation of diltiazem has been available for the treatment of angina pectoris but has not been comprehensively evaluated in hypertension. This study's aim was to evaluate the efficacy, dose-response characteristics, and duration of action of tablet (prompt-release) diltiazem in mild to moderate hypertension. Three placebo-controlled trials were designed. The first (trial #1) evaluated the dose response of 120, 240, and 360 mg/day (q12h regimen) of diltiazem in parallel fixed-dose fashion using hourly blood pressures. The second (trial #2) evaluated a q12h titration from 240 to 360 mg/day, which could be switched to q8h. The third (trial #3) evaluated a q8h titration from 180 to 270 to 360 mg/day, followed by conversion to a q12h regimen. The goal was a supine diastolic blood pressure of less than 90 mmHg and 10 mmHg less than baseline. With doses of diltiazem increasing from 120 to 240 to 360 mg/day, there was a progressive decrease in the average mean arterial pressure, describing a dose response with 120 mg/day as the ineffective dose. The peak effect for each dose regimen was found at 6 hours, with significant reductions lasting over 10 hours in the 240 mg/day and 360 mg/day groups. Peak plasma concentrations occurred at 3 hours. The residual effect at the trough of the 240 mg/day and 360 mg/day doses was 48% and 53% of the peak effect, respectively. When titration was carried out on a q8h regimen, both systolic and diastolic blood pressures were significantly decreased. When the regimen was switched from q8h to q12h, the effect was not maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of different cross-linking methods and processing parameters on drug release from hydrogel beads

“…This indicates that ionic cross-linking produced beads which were less rigid in structure and collapsed during drying, and may be ascribed to two reasons: less number of COOH groups introduced in the polymer chain by carboxymethylation (degree of substitution = 0.73) and inability of free Al 3+ ions to interact with the COOH groups. Unlike CaCl 2 , AlCl 3 ionizes in water to form hexaqua complex aluminum ion (AlCl 3 . Since free Al 3+ ions were not available in aqueous solution of AlCl 3 and charge on the aluminum complex ion was less, ionic cross-linking between the COOH groups and the aluminum complex ion was weak and produced less rigid hydrogel beads which collapsed during drying.…”

“…Diltiazem-HCl, a calcium channel blocker is a popular and effective drug for adequate control of hypertension [3] and angina pectoris [4]. However, because of short half-life of 3.5 h, the drug is administered three to four times a day [5].…”

In Vitro Dissolution Profiles of Two Diltiazem Tablet Formulations and a Compounded Capsule Formulation: A Comparative Study

“…Furthermore, a study (17) of diltiazem as monotherapy for the treatment of hypertension demonstrated that diltiazem immediaterelease tablets have good efficacy when taken three to four times a day.…”