Sustained Blood Pressure Control with Controlled‐Release Isradipine (Isradipine‐CR)

Abstract

The safety and efficacy, as measured by peak/trough blood pressure reduction, of a new, once-daily, controlled-release formulation of isradipine (isradipine-CR, ICR) were evaluated in patients with mild to moderate essential hypertension during a nine-week trial. After a 3-week placebo washout period, patients with a sitting diastolic blood pressure between 100 and 114 mm Hg were randomized to either 1 of 4 ICR treatment groups or placebo. Of 402 randomized patients, 384 completed the study (placebo = 77, ICR-5 mg = 76, ICR 10 mg = 76, ICR-15 mg = 78, and ICR-20 mg = 77). Peak and trough post-dose blood pressure responses and heart rates were monitored for both the sitting and upright positions. Blood chemistries, urinalyses, complete blood counts, and electrocardiograms were done during the study. Both sitting and upright blood pressure decreased with the 5-(P < .05), 10-, 15-, and 20-mg (P < .001) once-daily ICR doses. The peak blood pressure reduction for all ICR doses occurred at 8 to 10 hours post-dose. Maximum peak/trough blood pressure response, achieved with the 10-mg dose, was similar with that of 15 and 20 mg of ICR. No serious clinical or metabolic side effect were noted, except ankle edema, which was dose dependent but did not require discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on Verapamil

“…Crushing or dividing the tablet changes the delivery characteristics of the system such that it becomes an immediate-release preparation. 41,45,46 The osmotic pump contains 2 compartments: a polymeric push compartment and an osmotic drug core; the entire tablet is surrounded by a cellulosic membrane that is water-but not drug-or excipient-permeable. 44 The osmotic pump or gastrointestinal therapeutic system provides a form of zero-order drug delivery and is used with Procardia XL (Pfizer Inc), DynaCirc CR (Reliant Pharmaceuticals, Inc, Liberty Corner, NJ), and Covera-HS ( Figure 3).…”

“…44 The osmotic pump or gastrointestinal therapeutic system provides a form of zero-order drug delivery and is used with Procardia XL (Pfizer Inc), DynaCirc CR (Reliant Pharmaceuticals, Inc, Liberty Corner, NJ), and Covera-HS ( Figure 3). 41,45,46 The osmotic pump contains 2 compartments: a polymeric push compartment and an osmotic drug core; the entire tablet is surrounded by a cellulosic membrane that is water-but not drug-or excipient-permeable. 47 There is a laserdrilled opening on the drug side of the tablet to permit delivery of the drug as the polymeric push compartment expands.…”

“…Adapted with permission from Chrysant and Cohen. 46 The combination of the 2 medications is one of several options available for the management of supraventricular tachycardias. The concurrent use of verapamil and the α-blocker prazosin results in a significantly greater decrease in BP than when either drug is used alone.…”

“…Long-acting or sustainedrelease formulations of CCBs are less commonly associated with these side effects; the sustained-release formulations of CCBs are, however, more likely to be associated with dose-dependent peripheral edema ( Figure 6). 46 CCB-related peripheral edema is the consequence of greater arteriolar than venular dilation. This mismatch of dilation favors fluid extravasation as capillary pressures rise.…”

Safety and Efficacy of Therapeutically Equivalent Doses of Sustained‐Release Formulations of Isradipine and Felodipine

“…Two examples of the newer agents include sustained‐release isradipine (SR‐I) and sustained‐release felodipine (SR‐F), which are equipotent, 2 have an identical recommended starting dose (5 mg/d) and first‐step titration (10 mg/d), 3,4 and come in a once‐daily formulation that can effectively control blood pressure (BP). Despite their similarities, differences in observed trough/peak ratios between these two agents 3,5 suggest that SR‐I may be a more effective 24‐hour antihypertensive drug than SR‐F. Herein we report the results of a study conducted to determine whether subjects receiving SR‐F can be safely switched to SR‐I and whether substituting SR‐I for SR‐F improves the antihypertensive response in subjects currently being treated with SR‐F.…”