IMPORTANCE OF BLOOD-FLOW TO THE LOCAL-DISTRIBUTION OF DRUGS AFTER PERCUTANEOUS-ABSORPTION IN THE BIPEDICULATED DORSAL FLAP OF THE HAIRLESS RAT

In order to study the importance of cutaneous blood flow variations to percutaneous drug absorption and local distribution, a bipediculated dorsal flap was created in the hairless rat. This model allowed us to compare the percutaneous drug absorption on both sides of the flap, one with normal blood flow and the other with a reproducible blood flow decrease (60%) obtained by ligation of one pedicle. C-14-labelled compounds, progesterone (lipophilic), caffeine (amphiphilic) and urea (hydrophilic) were applied in ethanolic solution during 4 h on the two sides of the flap. When the cutaneous blood flow was lowered, the skin radioactivity increased greatly for caffeine (76% in superficial dermis, 67% in deep dermis), less for progesterone (37% in superficial dermis, 30% in deep dermis). For urea, no significant difference was observed between the two sides of the flap. Nevertheless, when the absorption of urea was promoted by application on stripped skin, radioactivity was greatly increased on the ligated side of the flap (240% in superficial dermis, 423% in deep dermis). Our results showed that a hydrophilic compound poorly absorbed (urea) was insensitive to cutaneous blood flow modifications whereas compounds readily absorbed (caffeine, amphiphilic; urea on stripped skin) or slightly absorbed (progesterone, lipophilic) exhibited local concentration phenomena in relation to cutaneous blood flow lowering.