The Relationship Between the Particle Size of Dicumarol and its Bioavailability in Dogs Part I. Capsules

Three different lots of 50 mg. capsules of dicumarol produced markedly different effects on the blood clotting mechanism in dogs. Upon microscopic examination of the content of the capsules, a relationship between the particle size of dicumarol and the dissolution rate, inhibition of normal prothrombin activity and plasma concentration was found.A general linear relationship was observed between the logarithm of drug concentration in plasma and the pharmacological effect of dicumarol produced by the three capsules. Also, as the area under the plasma concentration-time curve increased, so did the area under the percent inhibition of normal prothrombin activity-time curve produced by the three dicumarol capsules.