Bioavailability of a new oral methoxsalen formulation. A serum concentration and photosensitivity response study

Abstract

A new encapsulated liquid preparation of methoxsalen (soft gelatin capsule) was compared with the currently marketed hard gelatin capsule form and with an oral solution of methoxsalen in a random crossover design. Serial serum samples were collected from 25 healthy adult subjects and assayed by a high-performance liquid chromatography technique. Additionally, photosensitivity was determined by serial testing in 12 subjects. The soft-capsule formulation resulted in a 59% increase in extent of absorption and in a greater rate of absorption of methoxsalen than from the hard capsule. This was demonstrated by consistently higher peak serum concentrations (225 vs 199 ng/mL), which occurred at earlier times (1.8 vs 3.0 hours) following administration of the soft capsule. Photosensitivity testing confirmed these results, as photosensitivity was greater (9.53 vs 12.68 J/cm2) and reached a maximum earlier (1.5 vs 4.25 hours) following administration of the soft capsule. The soft capsule can be considered equivalent to the oral solution in both serum concentrations (peak concentration, 231 vs 225 ng/mL, and time of peak, 1.6 vs 1.8 hours) and photosensitivity response (maximum photosensitivity, 9.24 vs 9.53 J/cm2, and time of maximum photosensitivity, 1.32 vs 1.50 hours).