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INTERNATIONAL ANGIOLOGY

Rivista di Angiologia


Official Journal of the International Union of Angiology, the International Union of Phlebology and the Central European Vascular Forum
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International Angiology 1999 September;18(3):198-205

Copyright © 2000 EDIZIONI MINERVA MEDICA

lingua: Inglese

Clinical laboratory monitoring of a synthetic antithrombin agent, argatroban, using High Performance Liquid Chromatography and functional methods

Ahmad S., Iqbal O., Ahsan A., Hoppensteadt D. A., Lewis B. E., Walenga J. M., Fareed J.

From the Departments of Pathology and Pharmacology, and Cardiovascular Institute, Loyola University Chicago, Stritch School of Medicine, Maywood, USA


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Back­ground. Argat­ro­ban is a pep­ti­dom­i­met­ic inhib­i­tor of throm­bin which is in clin­i­cal ­trials for throm­bot­ic com­pli­ca­tions. Clot-based ­assays meas­ure the cumu­la­tive anti­co­ag­u­lant ­effect of argat­ro­ban and its metab­olites(s). To mon­i­tor the abso­lute con­cen­tra­tions of argat­ro­ban, a spe­cif­ic HPLC meth­od was devel­oped.
Meth­ods. Val­i­da­tion stud­ies includ­ed nor­mal vol­un­teers admin­is­tered with esca­lat­ing doses of argat­ro­ban (ARG 102 Study), ­patients under­go­ing cor­o­nary inter­ven­tion­al pro­ce­dures (ARG 310), and ­patients receiv­ing argat­ro­ban in con­juc­tion with strep­tok­i­nase for acute myo­car­dial infarc­tion (ARG 230). Plas­ma sam­ples were extract­ed with ace­ton­i­trile and recon­sti­tut­ed in a ­mobile phase. UV dete­cion was made at 333 nm. Cal­i­bra­trion ­curves were pre­pared with known stan­dards of argat­ro­ban in nor­mal human plas­ma.
­Results. The reten­tion time for argae­ro­ban was 6.0±0.5 min and the extrac­tion effi­cien­cy was >98% (r2=0.99). In the ARG102 Study, argat­ro­ban lev­els sere: 0.84±0.23 (day 1), 1.55±0.34 (day 2), 2.92±0.15 (day 3), and 3.04±0.49 (day 4). In the ARG310 trial, the mean argat­ro­ban lev­els were: 0.23+0.09 µg/ml (preinfu­sion), 5.77±0.92 µg/ml (postinfu­sion/intrapro­ce­dure), and 2.23±0.29 µg/ml (postpro­ce­dure). In the ARG 230 Study, the mean argat­ro­ban lev­els at 2-8 hrs were ­between 1.5-2.0 µg/ml. Upon com­ple­tion of the infu­sion, a time-depen­dent clear­ance of argat­ro­ban was noted.
Con­clu­sions. Since hep­a­rin­iza­tion, hemo­di­lu­tion and hypo­fib­ri­nog­e­ne­mia due to throm­bol­y­sis influ­ence the clot­ting tests, abso­lute quan­ti­ta­tion of argat­ro­ban by HPLC in these ­patients pro­vides a more reli­able means of mon­i­tor­ing this anti­co­ag­u­lant and helps in the dos­age-opti­mi­za­tion of this agent. The cur­rent HPLC meth­od is of value in the mon­i­tor­ing of ­paients who are simul­ta­ne­ous­ly admin­is­tered with throm­bo­lyt­ic drugs.

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