In Vivo Percutaneous Absorption of Hydrocortisone: Multiple-Application Dosing in Man

Percutaneous absorption of hydrocortisone was measured in six healthy adult men from whom informed consent had been obtained. The study compared a single topical dose to multiple-topical dose treatments (one vs three applications) on the same day. ¹⁴C-Labeled hydrocortisone in acetone was applied to 2.5 cm² of ventral forearm skin and protected with a nonocclusive polypropylene chamber. The amount of ¹⁴C measured in urine collected over 7 days was used to determine hydrocortisone absorption. The treatments, performed 2 to 3 weeks apart, each utilized adjacent sites on the same individuals. A single dose of 13.33 µg/cm² delivered 0.056 µg/cm² of hydro-cortisone through the skin. When the single dose was tripled to 40 µg/cm², the amount delivered through the skin increased by nearly three times, from 0.056 to 0.140 µg/cm²; the expected delivery was 3 x 0.056 µg/cm² = 0.168 µg/cm². Three serial doses of 13.33 µg/ cm² (total, 40 µg/cm²) were also expected to deliver 0.168 µg/cm² with or without soap and water washing between doses, but the observed amount of hydrocortisone delivered through the skin significantly exceeded our expectations. This indicates that multiple-dosing treatments resulted in a significant increase in bioavailability. It is postulated that increased vehicle application and washing dissolved and mobilized previously dosed hydrocortisone and increased bioavailability.