Pharmacokinetics of Cidofovir During Continuous Venovenous Hemofiltration

Pharmacokinetics of Cidofovir During Continuous Venovenous Hemofiltration

Cidofovir is an acyclic nucleotide analog with broad-spectrum antiviral activity against herpesviruses. Its potency in inhibiting HCMV has been shown in conventional in vitro studies. It is approved for the systemic treatment of human cytomegalovirus (HCMV) retinitis in patients with AIDS and as a second line therapy for HCMV infections not responding to ganciclovir or foscarnet.

In intensive care patients continuous venovenous haemofiltration (CVVH) is a well-established extracorporal renal replacement therapy with a high clearance rate.

Pharmacokinetic studies of antifungal agents in critically ill patients treated with CVVH are rare. Elimination of any given drug by renal replacement therapy is determined by several major factors which are membrane specific, due to physico-chemical properties of the drug and characteristics of the renal replacement technique used.

Study objective The trial is conducted to investigate the pharmacokinetics of cidofovir during CVVH in critically ill patients. It is suspected that Hemofiltration will influence cidofovir plasma levels.

Inclusion Criteria:

• Age 18 to 75 years
• Suspected of proven HCMV infection
• Suspected or proven resistancy of HCMV to the first line therapy (ganciclovir / foscarnet).
• Continuous venovenous hemodiafiltration (CVVHDF) due to acute or chronic renal failure.

Exclusion Criteria:

• Known history of hypersensitivity to cidofovir or probenecid.
• An expected survival of less than three days.
• Known alcohol dependency, epilepsy, pregnancy or liver failure.
• Infection with a ganciclovir or foscarnet susceptible HCMV strain