Hydrolysis of hydrocortisone 17-butyrate 21-propionate by cultured human keratinocytes.

Hydrolysis of 17-butyrate 21-propionate (HBP) by human keratinocytes was studied using an in vitro system. In the culture of human keratinocytes 1.308 nmole/ml of hydrocortisone 17-butyrate (de-esterified HBP at the position of 21) was found at 1 h after the addition of 10 nmole/ml HBP. At 6 h most of HBP was de-esterified to become HB17 and a small amount of hydrocortisone 21-propionate (de-esterified HBP at the position of 17) was detected. Hydrocortisone (HC) was not detectable. These results indicate that when HBP is applied on the skin, it is hydrolyzed at the position of 21, and reaches the dermis where it finds the way to get into the systemic circulation. The intracellular concentration of HBP was estimated to be more than 5 times its extracellular concentration and its accumulation was higher than HC. These results were discussed in relation to the potentiation of local antiinflammatory action and the reduction of systemic effects of topical glucocorticoid.