Peramivir Pharmacokinetics in Two Critically Ill Adults with 2009 H1N1 Influenza A Concurrently Receiving Continuous Renal Replacement Therapy

Study Objective. To determine the pharmacokinetics of intravenous peramivir-an investigational neuraminidase inhibitor for the treatment of 2009 H1N1 infection or nonsubtypable influenza A thought to be the 2009 H1N1 virus in patients concurrently receiving continuous renal replacement therapy (CRRT). Design. Pharmacokinetic analysis. Setting. Critical care unit at a university-affiliated hospital. Patients. Two critically ill women with 2009 H1N1 influenza A treated with compassionate-use intravenous peramivir administered as a daily infusion of 600 mg over 30 minutes while receiving continuous venovenous hemodiafiltration (CVVHDF), a form of CRRT. Measurements and Main Results. Plasma samples were collected from the two patients before and 30 minutes after the fourth (first patient) and ninth (second patient) peramivir infusion to estimate minimum (C-min) and maximum (C-max) plasma concentrations, respectively. Two additional postinfusion concentrations were measured from each patient to estimate noncompartmental pharmacokinetic parameters of peramivir while receiving CVVHDF. In the two patients, respectively, C-min was 2170 and 251 ng/ml, C-max was 18,400 and 20,300 ng/ml, area under the plasma concentration time curve from 0-24 hours (AUC(0-24)) was 178,000 and 94,400 ng.hour/ml, drug clearance was 56 and 106 ml/minutes, and plasma half-life was 7.6 and 3.7 hours. The volume of distribution adjusted for ideal body weight at steady state was 0.51 and 0.54 L/kg, respectively. Conclusion. The first patient had a slower peramivir plasma clearance compared with the second patient, but both patients had higher peramivir clearances as calculated from AUC(0-24) than those predicted by CRRT. Thus, the dosage of intravenous peramivir was appropriate in these patients. Additional pharmacokinetic data are needed to confirm these results and help guide dosing in patients receiving various forms of CRRT.