The pharmacokinetics of subcutaneous enoxaparin in end-stage renal disease

Study Objective. To evaluate the pharmacokinetics of enoxaparin in end-stag e renal disease (ESRD), and determine if dosage reduction is necessary to m aintain antifactor Xa activity concentrations within the therapeutic range. Design, Prospective, single-dose pharmacokinetic study Setting. University-affiliated general clinical research center. Patients. Eight nonthrombosed patients with ESRD requiring hemodialysis. Intervention. All subjects received a single dose of enoxaparin sodium 1 mg /kg subcutaneously and had serial plasma antifactor Xa activity concentrati ons measured over 24 hours. Measurements and Main Results. The pharmacokinetics of enoxaparin were dete rmined from plasma antifactor Xa activity concentrations, and various multi ple-dose regimens were simulated. After administration of the drug, total b ody clearance was 14.6 ml/minute and there was a 2-fold prolongation in ant ifactor Xa activity half-life compared with values reported in healthy subj ects. All other pharmacokinetic parameters were similar to those in healthy subjects and patients with chronic renal insufficiency An accumulation rat io of 1.6 was estimated for a dosing interval of every 12 hours based on si ngle-dose pharmacokinetics. When various therapeutic regimens were simulate d to predict average steady-state antifactor Sa activity, standard enoxapar in dosages of 1 mg/kg subcutaneously every 12 hours and 1.5 mg/kg every 24 hours resulted in average steady-state concentrations within the therapeuti c range. Conclusions, Based on antifactor Xa activity ESRD has little effect on the pharmacokinetics of enoxaparin, and dosing adjustments are unnecessary