Bioequivalence of verapamil hydrochloride extended-release pellet-filled capsules when opened and sprinkled on food and when swallowed intact.
A study was performed to determine whether verapamil hydrochloride administered in extended-release pellet-filled capsules is bioequivalent to the same formulation administered by sprinkling the contents of the capsules onto food. Thirty-two healthy subjects participated in the randomized, two-way crossover study. In treatment A, the subjects swallowed the contents of a verapamil hydrochloride extended-release pellet-filled capsule, 240 mg, that had been sprinkled on applesauce. In treatment B, the subjects swallowed the same type of capsule intact. Blood samples were drawn at baseline, every hour for 10 hours, and at 12, 15, 24, 30, 36, and 48 hours after each dose administration. The plasma was analyzed for verapamil and norverapamil by high-performance liquid chromatography. The following calculations were performed: AUC0-48, AUC0-infinity, Cmax, tmax, and k. Results for the two treatments were compared by analysis of variance. There were no significant differences between the AUC0-48, AUC0-infinity, Cmax, tmax, and k for the two methods of dose administration. For verapamil the differences for all variables were less than 5%, and for norverapamil the differences were less than 4% for all variables except tmax (9.5%). The 90% confidence intervals were within acceptable limits for all variables except the norverapamil tmax comparison. Sprinkling the contents of extended-release pellet-filled capsules onto food provides verapamil hydrochloride that is bioequivalent to that obtained from the intact capsules.
Kozloski
G D
GD
Scientific Services, Lederle Laboratories, Pearl River, NY.
De Vito
J M
JM
Johnson
J B
JB
Holmes
G B
GB
Adams
M A
MA
Hunt
T L
TL
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002214:Capsules; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D005502:Food; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency; D014700:Verapamil / Q000008:administration & dosage / Q000493:pharmacokinetics*
D002214:Capsules; D003692:Delayed-Action Preparations; D014700:Verapamil