Single-Dose Pharmacokinetics of Cidofovir in Continuous Venovenous Hemofiltration

Abstract

ABSTRACTDosage recommendations for cidofovir are available for renally competent as well as impaired patients; however, there are no data for patients undergoing continuous renal replacement therapy. We determined the single-dose concentration-versus-time profile of cidofovir in a critically ill patient undergoing continuous venovenous hemofiltration (CVVH). One dose of 450 mg cidofovir (5 mg/kg) was administered intravenously due to a proven cytomegalovirus (CMV) infection and failure of first-line antiviral therapy. Additionally, 2 g of probenecid was administered orally 3 h prior to and 1 g was administered 2 h as well as 8 h after completion of the infusion. The concentrations of cidofovir in serum and ultrafiltrate were assessed by high-performance liquid chromatography. The peak serum concentration measured at 60 min postinfusion was 28.01 mg/liter at the arterial port. The trough serum level was 19.33 mg/liter at the arterial port after 24 h. The value of the area under the concentration-versus-time curve from 0 to 24 h was 543.8 mg · h/liter. The total body clearance was 2.46 ml/h/kg, and the elimination half-life time was 53.32 h. The sieving coefficient was 0.138 ± 0.022. Total removal of the drug was 30.99% after 24 h. Because of these data, which give us a rough idea of the concentration profile of cidofovir in patients undergoing CVVH, a toxic accumulation of the drug following repeated doses may be expected. Further trials have to be done to determine the right dosage of cidofovir in patients undergoing CVVH to avoid toxic accumulation of the drug.