Evaluation of two buflomedil tablet formulations in patients with atherosclerotic disease.
The bioequivalence of a 600-mg methocel tablet containing buflomedil hydrochloride in sustained-release form was determined relative to a 300-mg CAP/carbovax-coated tablet of buflomedil hydrochloride in immediate-release form. The tablets were given to 20 patients in a double-blind placebo-controlled clinical study with cross-over between the administration plans. The 300-mg tablets were given b.i.d., at 8 a.m. and 8 p.m. while the 600-mg tablets were taken once a day at 8 a.m. (+placebo at 8 p.m.). Plasma samples were collected at appropriate times up to 24 h after administration and were analyzed for buflomedil with a validated high-performance liquid chromatographic procedure. Results showed an overall significant mean difference in absorption rate between the two formulations. The mean tmax (5.5 +/- 3.5 h) for the 600-mg tablet was longer (P < 0.001) than the tmax value (1.8 +/- 0.8 h) seen after administration of the first 300-mg tablet. Analysis of AUC(O-infinity) values indicated that the sustained-release preparation (32.1 +/- 20.7 micrograms/ml h) was not significantly different from the 300-mg tablet b.i.d. (28.7 +/- 16.0 micrograms/ml h). Furthermore, it was seen that single administration of a 600-mg sustained-release tablet of buflomedil hydrochloride delivered the same amount of total drug as a 300-mg tablet given twice a day.
Molinaro
M
M
Department of Pharmacology, IRCCS, Policlinico S. Matteo, Pavia, Italy.
Regazzi
M B
MB
Raffaghello
S
S
Buggia
I
I
Iacona
I
I
Graziani
P
P
Specchia
G
G
Melzi D'eril
G
G
D000368:Aged; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism*; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D011759:Pyrrolidines; D013607:Tablets; D014665:Vasodilator Agents; C010651:buflomedil