PHARMACOKINETIC DESIGN FOR USE IN PRECLIN ICAL PHASE - APPLICATION TOTHE STUDY OF AN ANTHRACENONE

T-514 is a toxic substance of Karwinskia humboldtiana which has been d escribed as a possible anticancer agent. An animal model (New Zeland w hite rabbit) was selected for pharmacokinetic studies that would allow the performance of surgical techniques to catherize central vessels i n order to obtain blood samples at short time intervals. A nonlinear r egression analysis method was used to fit the plasmatic concentration data to a multiexponential mathematical function; a computer program b ased on Marquant's iterating algorithm was used to fit the experimenta l curves. In the present work we show the advantage of introducing two catheters of different diameters in the jugular vein using modificati ons of the Seldinger and Braunule techniques: a catheter of small diam eter (18 G) is used to introduce the drug and a larger diameter cathet er facilities a rapid sampling of blood (two mL/s) which is essential to determine the initial phase of the distribution process (alpha phas e). The behavior of T-514 corresponded to a two-compartment model with a biexponential equation C=0.35e-0.13(t-2) + 0.17 e-0.03(t-2).