POSTABSORPTION CONCENTRATION PEAKS WITH BRAND-NAME AND GENERIC VERAPAMIL - A DOUBLE-BLIND, CROSSOVER STUDY IN ELDERLY HYPERTENSIVE PATIENTS

The pharmacokinetic actions, bioequivalence, and cardiovascular effect s of two verapamil products were studied in a randomized, double-blind , crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate- release verapamil in 120-mg twice-daily doses for 14 days. Blood press ures, heart rates, P-R intervals, and serum concentrations of R-/S-ver apamil and norverapamil were measured multiple times in patients durin g the last day of each therapy. Median blood pressure decreased more w ith generic verapamil than with the brand-name drug, with the largest difference occurring at 0.5 hours (137/74 mmHg versus 144.5/80.5 mmHg; P = 0.05 and 0.091, respectively). Pharmacokinetic parameters were no t different for the two products (P < 0.10). However, the generic prod uct, compared with the brand-name drug, had mean area under the concen tration-time curve (time 0 to 12 hours) ratios (90% CI) of 1.09 (0.78- 1.52), 1.16 (0.87-1.55) and 1.11 (0.81-1.52) for R-, S-, and total ver apamil. Seventy concentration peaks (31 with the brand-name drug, 39 w ith the generic drug) appeared between 8 and 24 hours. Median percenta ges of increase of these peaks, compared with those of previous concen trations, were 48.3% and 36.3% for brand-name and generic drugs, respe ctively. Fifty of the 70 peaks (71%) were associated with a stereospec ific concentration peak of norverapamil and, temporally, with meals. O ur findings suggest that whereas the two verapamil products may not be bioequivalent by Food and Drug Administration criteria, the observed differences in effects were not clinically significant in this elderly population. Multiple concentration peaks after absorption were observ ed in all patients with both verapamil products and were perhaps relat ed to enterohepatic recirculation.