Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Simultaneous monitoring of argatroban and its major metabolite using an HPLC method: Potential clinical applications
Autore:
Ahmad, S; Ahsan, A; George, M; Iqbal, O; Jeske, WP; McKenna, R; Lewis, BE; Walenga, JM; Fareed, J;
Indirizzi:
Loyola Univ, Stritch Sch Med, Dept Pathol, Maywood, IL 60153 USA Loyola Univ Maywood IL USA 60153 Med, Dept Pathol, Maywood, IL 60153 USA Loyola Univ, Stritch Sch Med, Dept Pharmacol, Maywood, IL 60153 USA LoyolaUniv Maywood IL USA 60153 d, Dept Pharmacol, Maywood, IL 60153 USA Loyola Univ, Stritch Sch Med, Cardiovasc Inst, Maywood, IL 60153 USA Loyola Univ Maywood IL USA 60153 , Cardiovasc Inst, Maywood, IL 60153 USA
Titolo Testata:
CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS
fascicolo: 4, volume: 5, anno: 1999,
pagine: 252 - 258
SICI:
1076-0296(199910)5:4<252:SMOAAI>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
SYNTHETIC THROMBIN INHIBITOR; HEPARIN; ANTICOAGULANT; HIRUDIN; HIRULOG;
Keywords:
argatroban; M1-metabolite; HPLC; antithrombin drugs; heparin-induced thrombocytopenia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
15
Recensione:
Indirizzi per estratti:
Indirizzo: Fareed, J Loyola Univ, Med Ctr, Thrombosis & Hemostasis Res Labs, 2160 S 1st Ave, Maywood, IL 60153 USA Loyola Univ 2160 S 1st Ave Maywood IL USA 60153 od, IL 60153 USA
Citazione:
S. Ahmad et al., "Simultaneous monitoring of argatroban and its major metabolite using an HPLC method: Potential clinical applications", CL APPL T-H, 5(4), 1999, pp. 252-258

Abstract

Argatroban is a peptidomimetic inhibitor of thrombin that is currently undergoing extensive clinical trials as a heparin substitute for thrombotic complications. Argatroban is readily metabolized into a major derivative, MI,that has pharmacological characteristics distinct from its parent compound. The currently available clot-based assays measure the cumulative anticoagulant effect of argatroban and its metabolite(s). Available HPLC methods donot differentiate between argatroban and MI-metabolite. A modified method was developed to simultaneously quantitate MI-metabolite and argatroban in biological fluids. Initial validation studies for the method included clinical trials of argatroban in patients with heparin-induced thrombocytopenia,(ARC 911 Study) and coronary interventional procedures (ARG 310 Study). Plasma samples were extracted with acetonitrile and reconstituted in a mobilephase. Calibration curves were prepared by running known standards of: argatroban and MI-metabolite in normal human plasma. Ultraviolet detection wasmade at 320 nm. The retention times for argatroban and MI-metabolite peakswere found to be 10.5 +/- 0.3 minutes and 3.9 +/- 0.1 minutes, respectively. The extraction efficiency was > 95% (r(2) = 0.99). In heparin-induced thrombocytopenia patients with major bleeding complications (n = 30), the relative increase in M1-metabolite compared to argatroban varied widely (two- to eight-fold). The mean concentration of argatroban during the steady infusion period was found to be 0.7 +/- 0.35 mu g/mL, and for M1-metabolite, itwas 5.5 +/- 2.8 mu g/mL. Proportionate results were not seen when higher dosages of argatroban were administered (coronary angioplasty studies). Argatroban and M1-metabolite levels also compared well with the results in global clotting assays. Owing to the simultaneous quantitation of argatroban and Mi-metabolite, this method provides a rapid assessment of the pharmacokinetics and pharmacodynamics of argatroban. The differential quantitation maybe useful in the assessment of relative metabolic turnover of argatroban that can be related to the hepatic and renal functions in a given patient.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 15:13:43