Desirudin Dosing and Monitoring in Moderate Renal Impairment
- 1 June 2010
- journal article
- Published by Wiley in The Journal of Clinical Pharmacology
- Vol. 50 (6), 614-622
- https://doi.org/10.1177/0091270009350626
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.Keywords
This publication has 23 references indexed in Scilit:
- Relationship of Activated Partial Thromboplastin Time to Coronary Events and Bleeding in Patients With Acute Coronary Syndromes Who Receive HeparinCirculation, 2003
- Hirudin In Renal InsufficiencySeminars in Thrombosis and Hemostasis, 2002
- A Brief Introduction to Monte Carlo SimulationClinical Pharmacokinetics, 2001
- DesirudinDrugs, 2000
- Economic Evaluation of Desirudin vs Heparin in Deep Vein Thrombosis Prevention after Hip Replacement SurgeryPharmacoEconomics, 1998
- A Comparison of Recombinant Hirudin with a Low-Molecular-Weight Heparin to Prevent Thromboembolic Complications after Total Hip ReplacementThe New England Journal of Medicine, 1997
- A Comparison of Recombinant Hirudin with Heparin for the Treatment of Acute Coronary SyndromesThe New England Journal of Medicine, 1996
- Prevention of deep-vein thrombosis after total hip replacement: direct thrombin inhibition with recombinant hirudin, CGP 39393The Lancet, 1996
- Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors.JCI Insight, 1990
- Catabolism of therapeutic proteins and peptides with implications for drug deliveryAdvanced Drug Delivery Reviews, 1989