IN-VIVO DETERMINATION OF ZERO-ORDER ABSORPTION FROM A TRANSDERMAL GLYCEROL TRINITRATE SYSTEM

This report uses the Wagner-Nelson method to demonstrate that a trans dermal delivery system results in zero-order absorption of glycerol tr initrate. The Wagner-Nelson plots of Fraction Absorbed versus time (FA versus t) from 48 of a total of 60 plasma profiles were linear where the slope, k(o)/FD, averaged 0.0855 h-1 with a coefficient of variatio n of only 4.68%. Forty of the 48 Wagner-Nelson profiles had negative i ntercepts which averaged -0.0543 (range -0.00016 to -0.160) correspond ing to lag times averaging 0.619 h (range 0.002 to 1.62 h); the other 8 subjects had positive intercepts. Another method (C(ss)/AUC(infinity )) using standard steady-state equations is also described to estimate k(o)/FD for transdermal systems displaying zero-order absorption. Bot h methods arrived at similar values for the transdermal rate of absorp tion for glycerol trinitrate.