[Pharmacokinetic design for the preclinical phase. Application to the study of an anthracenone].
T-514 is a toxic substance of Karwinskia humboldtiana which has been described as a possible anticancer agent. An animal model (New Zeland white rabbit) was selected for pharmacokinetic studies that would allow the performance of surgical techniques to catheterize central vessels in order to obtain blood samples at short time intervals. A nonlinear regression analysis method was used to fit the plasmatic concentration data to a multiexponential mathematical function; a computer program based on Marquant's iterating algorithm was used to fit the experimental curves. In the present work we show the advantage of introducing two catheters of different diameters in the jugular vein using modifications of the Seldinger and Braunüle techniques: a catheter of small diameter (18 G) is used to introduce the drug and a larger one (16 G) to sample at different times. The larger diameter catheter facilitates a rapid sampling of blood (two mL/s) which is essential to determine the initial phase of the distribution process (alpha phase). The behavior of T-514 corresponded to a two-compartment model with a biexponential equation C = 0.35 e-0.13(t-2) + 0.17 e-0.03(t-2).
Adame-Reyna
M
M
Departamento de Farmacología, Facultad de Medicina, U.A.N.L., Monterrey, N.L., México.
Guerrero-Olazarán
M
M
Belmontes-Hernández
R
R
Viader-Salvadó
J M
JM
D000465:Algorithms; D000818:Animals; D000873:Anthracenes / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D001800:Blood Specimen Collection / Q000295:instrumentation / Q000379:methods*; D001825:Body Fluid Compartments; D002405:Catheterization, Central Venous; D002408:Catheters, Indwelling; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D007275:Injections, Intravenous; D011817:Rabbits / Q000097:blood* / Q000601:surgery; D012044:Regression Analysis; D012107:Research Design
D000873:Anthracenes; D000972:Antineoplastic Agents, Phytogenic; C075149:Karwinskia toxin T-514
Diseño farmacocinético de fase preclínica. Aplicación al estudio de una antracenona.