Verapamil and prazosin in essential hypertension: evidence of a synergistic combination?
An enhanced hypotensive effect has been observed in short-term studies of the combination of an alpha-adrenoceptor antagonist and a calcium channel blocker. This study further evaluates combined treatment with prazosin and verapamil in 12 essential hypertensives who had not responded satisfactorily to standard beta-blocker and thiazide diuretic regimens. After placebo treatment, patients received monotherapy with either prazosin or verapamil. The appropriate second drug was then added, and combination treatment was continued for 4 weeks. A series of 8 h study days was undertaken at the end of each treatment phase to assess blood pressure, heart rate, and pharmacokinetics. Both monotherapies caused significant reductions in blood pressure. For the prazosin group the average blood pressure on monotherapy was 146/81 mm Hg (supine) and 151/88 mm Hg (erect), and for the verapamil group the corresponding figures were 149/81 and 156/92 mm Hg. In both groups significant further reductions in blood pressure were observed during combination treatment: on average, 133/74 mm Hg (supine) and 130/77 mm Hg (erect) for the prazosin group and, respectively, 137/75 and 141/85 mm Hg for the verapamil group. The pharmacokinetics of verapamil were not altered by the coadministration of prazosin, but there were changes in the pharmacokinetics of prazosin, with significant increases in peak plasma concentrations and bioavailability. Prazosin and verapamil form a useful antihypertensive drug combination. The overall effect is partly due to an increase in the apparent bioavailability of prazosin but may also reflect a synergistic effect on reducing peripheral vascular resistance.
Elliott
H L
HL
University Department of Materia Medica, Stobhill General Hospital, Glasgow, Scotland.
Meredith
P A
PA
Reid
J L
JL
D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011224:Prazosin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011897:Random Allocation; D014700:Verapamil / Q000493:pharmacokinetics / Q000627:therapeutic use*
D014700:Verapamil; D011224:Prazosin