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Rivista di Angiologia
Official Journal of the , the International Union of Phlebology and the
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
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International Angiology 1999 Settembre;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.