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A Journal on Angiology

Official Journal of the International Union of Angiology, the International Union of Phlebology and the Central European Vascular Forum
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 0,899

Frequency: Bi-Monthly

ISSN 0392-9590

Online ISSN 1827-1839


International Angiology 1999 September;18(3):198-205


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

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.

language: English


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