Acute Renal Failure, Cytomegalovirus Retinitis
Conditions
Keywords
cidofovir, cvvh, renal replacement therapy, HCMV, Pharmacokinetics of cidofovir during CVVH, continuous venovenous hemofiltration
Brief summary
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.
Interventions
OTHERCidofovir pharmacokinetics
Blood samples were drawn before and 15, 30, 60, 120, 240, 360, 720 and 1440 minutes after the start of the cidofovir infusion. Plasma and ultrafiltration samples were collected from the outlet of the ultrafiltrate compartment of the hemofilter.
Sponsors
University of Vienna
Medical University of Vienna
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AreaUnderCurve (AUC) | 24 hours | AUC (plasma concentration) of cidofovir during 24 hours of hemofiltration |
Secondary
| Measure | Time frame |
|---|---|
| maximum and minimum plasma concentration (Cmax, Cmin) of cidofovir during hemofiltration | 24 hours |
| total body clearance (Cltot) of cidofovir during hemofiltration | 24 hours |
| half-life (t1/2) of cidofovir during hemofiltration | 24 hours |
| sieving coefficient of cidofovir during hemofiltration | 24 hours |
| elimination fraction of cidofovir during hemofiltration | 24 hours |
| hemofiltration clearance (ClHF) of cidofovir during hemofiltration | 24 hours |
Countries
Austria
Outcome results
None listed