Pharmacokinetics of Peramivir in an Adolescent Patient Receiving Continuous Venovenous Hemodiafiltration

Abstract

Critically ill patients requiring renal replacement therapy commonly experience pharmacokinetic alterations. This case report describes the pharmacokinetics of peramivir (Rapivab, BioCryst Pharmaceuticals, Inc, Durham, NC), the first US Food and Drug Administration-approved intravenous neuraminidase inhibitor for the treatment of influenza, in an adolescent patient receiving continuous renal replacement therapy (CRRT). A 49.5-kg, 17-year-old Caucasian female presented with fever, cough, and persistent hypoxia. She quickly progressed to acute respiratory and renal failure in the setting of viral septic shock as a result of a severe influenza H1N1 infection. On hospital day 3, therapy was switched from oseltamivir (Tamiflu, Roche Laboratories Inc, Nutley, NJ) to peramivir owing to the concern for inadequate enteral absorption. On the third day of peramivir treatment, at a dose of 200 mg daily, peramivir serum concentrations revealed a smaller peak concentration, larger volumes of distribution, similar 24-hour area under the curve, and a shorter half-life as compared to adult patients with normal renal function. This illustrated the significant differences in pharmacokinetics when administered in the setting of CRRT. The patient had resolution of viral infection as evidenced by negative respiratory viral panel polymerase chain reaction at hospital day 14 and was eventually discharged at her baseline.

Treatment of influenza virus-related critical illness during continuous renal replacement therapy: take caution with dosing

“…In practice, as the plasma protein unbound fraction approaches 1 (as is the case with peramivir) and the molecular weight of the drug is low (below 20,000 Da), the sieving coefficient can be estimated to be 1 [3]. As a consequence, in this case report, the dosage scheme (200 mg daily) achieved a smaller serum peak concentration, larger volume of distribution, and a shorter half-life, illustrating the significant differences in pharmacokinetic (PK)/ pharmacodynamic (PD) target attainment when drugs are administered in the setting of continuous venovenous hemodiafiltration (CVVHDF) [2]. Scheetz et al recommend a steady-state concentration of 17,078 ng/ mL, which was averaged from peak and trough concentrations in adult patients with normal renal function [4].…”

“…The question that arises is the following: what is the dose to be given during continuous renal replacement therapy (CRRT)? According to the manufacturer's recommendations, the dose should be adjusted in line with the degree of reduction in creatinine clearance [2]. In a recent case report by Dillon et al, a dose of 200 mg daily, the recommended dose for patients with creatinine clearance of 30-49 mL/min, was given to a patient with acute kidney injury (AKI) managed with CRRT [2].…”

“…According to the manufacturer's recommendations, the dose should be adjusted in line with the degree of reduction in creatinine clearance [2]. In a recent case report by Dillon et al, a dose of 200 mg daily, the recommended dose for patients with creatinine clearance of 30-49 mL/min, was given to a patient with acute kidney injury (AKI) managed with CRRT [2]. In practice, as the plasma protein unbound fraction approaches 1 (as is the case with peramivir) and the molecular weight of the drug is low (below 20,000 Da), the sieving coefficient can be estimated to be 1 [3].…”

“…Scheetz et al recommend a steady-state concentration of 17,078 ng/ mL, which was averaged from peak and trough concentrations in adult patients with normal renal function [4]. Based on this recommendation, the patient reported by Dillon et al would have required more than 800 mg given the CRRT settings [2,4]. Doses of peramivir during CRRT vary from 200 to 800 mg per day in various case reports.…”

Evaluation of Baloxavir Marboxil and Peramivir for the Treatment of High Pathogenicity Avian Influenza in Chickens

“…For BXM, the blood was collected at 0, 8, 24, and 48 h post-administration (hpa), whereas for PR it was collected at 0, 0.5, 2, and 8 hpa. The duration of blood sampling was different for BXM and PR treatment given the long plasma half-life previously reported for BXM in humans [25] and the shorter plasma half-life reported for PR in mice [26] and humans [27].…”