Study objective: To determine if there are greater differences in bioavailability of generic verapamil at steady state in elderly patients than in healthy young subjects.
Design: Double-blind, randomized, three-way crossover study.
Setting: Clinical research center at a general teaching hospital.
Subjects: Eight young, healthy subjects between ages 18 and 45 years, and eight elderly, hypertensive patients over 65 years of age.
Interventions: Each participant was randomly assigned to receive brand-name verapamil or one of two generic preparations. Young subjects received each of the three preparations 80 mg twice/day for 7 days separated by a 1-week washout. Elderly patients took the three preparations for 21 days. Serum drug levels and blood pressure were measured and electrocardiograms performed 13 times after the last dose of drug.
Main results: In young subjects, the pharmacokinetics and pharmacodynamics of the three preparations were nearly identical. There was, however, a great deal of variability in the bioavailability of the generic products. In the elderly patients, one generic product had a maximum serum concentration and area under the curve that were 77% and 43% greater, respectively, than the brand-name product (p < 0.02). Assessments of bioequivalency (based on confidence intervals) demonstrated that this generic drug's bioavailability was from 4-118% and peak serum concentration from 10-139% greater than the brand-name drug. This was associated with greater prolongation of the PR intervals.
Conclusions: A generic verapamil product that is bioequivalent in young subjects may not be bioequivalent in elderly subjects. Testing of drugs with complex pharmacokinetics in young subjects may not reliably predict the clinical outcomes in elderly hypertensive patients.