The effect of the dosage form on serum levels of indoxole.

Abstract

The influence of dosage form on serum levels of indoxole (2,3‐bis‐[p‐methoxyphenyll]‐indole), an anti‐inflammatory agent with low water solubility, was studied. Serum concentrations (fluorometric assay) were observed for 16 hours after the last dose in a short‐term multiple‐dose tolerance study when the compound was administered orally at four dose levels in Lipomul‐Oral emulsion. A good dose response was obtained when the average serum concentrations of individual subjects in the last dosage interval were plotted against the milligram per kilogram dose. Serum concentrations were also measured after oral administration at two dose levels in four different dosage forms. The order of serum level response was: Lipomul‐Oral emulsion ≃ soft elastic capsule 〉 aqueous suspension 〉 powder in a capsule. Potency estimates were 1.00: 1.10: 0.47: 0.16 following the first dose and 1.00: 0.72: 0.27: 0.16 following the sixth dose for the emulsion, soft elastic capsule, aqueous suspension, and powder in a capsule, respectively. Additional information is reported and discussed. The advantage of defining the serum level of a drug after the first dose and during a dosage interval at the equilibrium state is pointed out. The attempt to measure peaks and nadirs of drug concentration in the blood in multiple dose studies is less desirable than the method described above.