Abstract
Malotilate (diisopropyl-1, 3-dithio1-2-ylidenemalonate) exists in two polymorphic forms, designated A and B. The transformation from A to B easily occurs at relatively low temperatures. Since different crystalline forms of a drug may influence its absorption and hence its therapeutic efficacy, two crystalline forms of malotilate (A and B) were assessed in 20 healthy male subjects using a two-way cross-over design. The concentration-time curve was shifted slightly to the right in the group that received the B form; however, there were no significant differences in the AUC, Cmax, and tmax between the two groups. Statistical evaluation of the data involved an analysis of variance for a cross-over design (ANOVA). This revealed significant differences for “Time Periods” and “Between Subjects, ” but not for “Group or Sequence” or “Drugs.” With 95% confidence, the confidence intervals of each parameter satisfied the criteria for AUC but not for Cmax and tmax. From the data obtained and taking into consideration their clinical use, we conclude that both the A and B forms of malotilate are bioequivalent.
