EVALUATION OF 2 BUFLOMEDIL TABLET FORMULATIONS IN PATIENTS WITH ATHEROSCLEROTIC DISEASE

The bioequivalence of a 600-mg methocel tablet containing buflomedil h ydrochloride in sustained-release form was determined relative to a 30 0-mg CAP/carbovax-coated tablet of buflomedil hydrochloride in immedia te-release form. The tablets were given to 20 patients in a double-bli nd placebo-controlled clinical study with cross-over between the admin istration 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. (+place bo at 8 p.m.). Plasma samples were collected at appropriate times up t o 24 h after administration and were analysed for buflomedil with a va lidated high-performance liquid chromatographic procedure. Results sho wed an overall significant mean difference in absorption rate between the two formulations. The mean t(max) (5.5 +/- 3.5 h) for the 600-mg t ablet was longer (P<0.001) than the t(max) value (1.8 +/- 0.8 h) seen after administration of the first 300-mg tablet. Analysis of AUC(0-inf inity) values indicated that the sustained-release preparation (32.1 /- 20.7 mug/ml h) was not significantly different from the 300-mg tabl et b.i.d. (28.7 +/- 16-0 mug/ml h). Furthermore, it was seen that sing le administration of a 600-mg sustained-release tablet of buflomedil h ydrochloride delivered the same amount of total drug as a 300-mg table t given twice a day.