Metabolism of propranolol during percutaneous absorption in human skin.

This in vitro study evaluated the extent of the absorption and metabolism of propranolol in human skin from four sources. Between 10.4 +/- 3.1 and 36.6 +/- 2.6% of the applied dose was absorbed; however, only a small portion (between 4.1 +/- 0.9 and 16.1 +/- 1.3%) of the dose permeated through the skin. Naphthoxyacetic acid formed during percutaneous absorption was located in the skin supernate. 4'-Hydroxypropranol was formed during percutaneous absorption and by skin microsomes. In addition, the microsomes biotransformed propranolol to norpropranolol. The retention of some of the absorbed drug and metabolites in the skin could explain the low plasma concentration and irritation observed following topical application of propranolol.