title: Desirudin dosing and monitoring in moderate renal impairment.
abstract: Desirudin is a renally eliminated direct thrombin inhibitor approved to prevent venous thromboembolism. Empiric dosage adjustment and activated partial thromboplastin time (aPTT) monitoring in patients with moderate renal impairment are recommended, but supportive data are lacking. The objective of this study was to evaluate appropriate desirudin dosing in moderate renal impairment and the effect of desirudin on aPTT in moderate renal impairment. Desirudin plasma concentration and aPTT data were extracted from 6 studies. Participants with normal renal function or moderate renal impairment (creatinine clearance [ClCr] 31-60 mL/min) were included. Pharmacokinetic and Monte Carlo simulations were done. After administration of desirudin 15 mg every 12 hours subcutaneously (SC) to steady state, peak desirudin concentrations were 35 and 47 nmol/L in the normal and moderate renal function groups, respectively. Monte Carlo simulations found median 2-hour C(max) concentrations of 51.7 nmol/L in normal renal function and 52.4 nmol/L in moderate renal impairment. Desirudin exhibits a linear relationship when the square root of desirudin concentration is plotted versus the aPTT ratio (r(2) = 0.76). These analyses support the dosing of desirudin at 15 mg every 12 hours SC without aPTT monitoring in patients with moderate renal impairment.
authors.affiliation: Bertino Consulting, 3078 New Williamsburg Drive, Schenectady, NY 12303-5381, USA. nafziger@ix.netcom.com
authors.forename: Anne N
authors.initials: AN
authors.lastname: Nafziger
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Bertino
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D006629:Hirudins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D009010:Monte Carlo Method; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D051437:Renal Insufficiency / Q000097:blood*
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; C060225:desirudin