Transdermal absorption and topical bioavailability of coumarin.

Coumarin was administered I.V., P.O. and topically to male Sprague-Dawley rats. The concentration-time profile after I.V. administration could be best described by an open-two compartment model. After P.O. administration the fraction of drug absorbed was 0.21 +/- 0.08 (S.D.). 1 g of hydrophilic ointment (U.S.P. XIX) containing 5% w/w of coumarin was applied on the shaven back skin. When the area of application was 4.91 cm2 the drug was absorbed in a zero-order fashion. The fraction of administered drug absorbed in 6 h was 0.086 +/- 0.02 (S.D.). Increasing the area of application to 30.0 cm2 resulted in deviation from the zero-order absorption characteristic. This is attributed to decrease in the concentration gradient as more drug is absorbed and to the change in formulation characteristics as a function of time. The fraction of drug absorbed in 24 h was 0.66 +/- 0.21 (S.D.).