Antihypertensive properties of the novel calcium antagonist mibefradil (Ro 40-5967): a new generation of calcium antagonists? Mibefradil International Study Group.
Preclinical and initial clinical studies suggest that the novel calcium antagonist mibefradil has a unique combination of properties. Mibefredil was evaluated in a multicenter, double-blind, placebo-controlled, parallel group trial. After 4 weeks of a placebo run-in period, 202 eligible patients with mild to moderate hypertension were randomized to receive doses of 25, 50, 100, or 150 mg mibefradil or placebo once a day for 4 weeks. Blood pressure and heart rate were measured repeatedly at trough and peak (24 and 2 to 6 hours postdose, respectively) at the end of each period. Concentration-effect relationships were evaluated at trough on the last treatment day. A significant (P<.01 versus placebo) drop in blood pressure (diastolic and systolic) was observed at trough and peak in all mibefradil groups, with a trough-peak ratio greater than 0.8, high response rate, and a significant dose-response relationship (P<.001). The full antihypertensive effect of mibefradil was achieved within 1 to 2 weeks and was associated with a slight dose-dependent decrease in heart rate and increase in PQ time. Clear dissociation was observed between the effect on blood pressure and PQ time when concentration-effect relationships were evaluated. These results indicate that mibefradil is an effective and well-tolerated antihypertensive compound at doses of 25, 50, and 100 mg once daily. The incidence of treatment-related adverse events observed in the 25-, 50-, and 100-mg dose groups was lower than in the placebo group, but it was slightly higher in the 150-mg dose group, and three patients from this group were prematurely withdrawn because of an adverse event.
Bernink
P J
PJ
Martini Ziekenhuis, Groningen, The Netherlands.
Prager
G
G
Schelling
A
A
Kobrin
I
I
D000293:Adolescent; D000328:Adult; D001562:Benzimidazoles / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D020748:Mibefradil; D008875:Middle Aged; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage*
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D020748:Mibefradil