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Alterations in absorption of dicumarol by various excipient materials.

A plasma level study was conducted in dogs to determine the effects of various excipient materials on the absorption of dicumarol. The drug was combined with the excipients by an equilibration process and administered orally. Plasma concentrations of dicumarol after administration with excipients were compared to control levels produced by the drug given alone. Significant differences in the plasma levels of dicumarol were observed with six of the 10 excipients used in the study. Significantly higher plasma levels (up to 180% of control values) were observed when dicumarol was administered with magnesium oxide or hydroxide. This effect may be due to chelate formation because the magnesium chelate of dicumarol produced higher plasma levels of dicumarol than the drug administered alone. Dicumarol administration with talc, colloidal magnesium aluminum silicate, aluminum hydroxide, or starch resulted in significantly lower plasma levels of the drug. It is suggested that these types of interactions may be an explanation for differences in the bioavailability of dicumarol from different dosage formulations.