title: Influence of albumin dialysis on pharmacokinetics of amphotericin B colloidal dispersion and amphotericin B lipid complex.
abstract: Albumin dialysis (AD) is a therapeutic option in severe cholestatic liver failure. However, it can significantly enhance drug elimination. Pharmacokinetic data on antimicrobial agents--in particular on antimycotics--administered under this clinical condition are very sparse. Therefore, amphotericin B (AMB) plasma concentrations were measured in two critically ill patients who were treated with AD because of severe cholestatic liver failure and were prescribed lipid formulated AMB--either AMB colloidal dispersion (ABCD) or AMB lipid complex (ABLC)--for suspected invasive fungal infection. AD was performed with the molecular adsorbent recirculating system (MARS). Lipid-associated and liberated AMB were separately quantified on and off AD. The clearance of the liberated AMB fraction was not essentially affected (ABLC) or moderately enhanced during AD by a factor of 2.5 (ABCD). The clearance of the lipid-formulated fraction was increased by a factor of 4 during AD (ABCD) or was similar (ABLC) on and off AD. Despite the fact that there was a four-fold higher clearance of the lipid-formulated fraction of ABCD, the clinically relevant area under the concentration time curve of the liberated AMB fraction was only moderately changed (by 37% in ABCD, 70% in ABLC) during AD. Thus, the effect of AD on lipid formulated AMB appears to be moderate. A daily dose of 5 mg/kg will probably lead to adequate plasma levels in patients on AD.
authors.affiliation: Clinical Pharmacokinetics Unit, Laboratory of Inflammation Research Medical Intensive Care Unit, Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weiler
authors.forename: Helene
authors.initials: H
authors.lastname: Vogelsinger
authors.forename: Michael
authors.initials: M
authors.lastname: Joannidis
authors.forename: Stefan
authors.initials: S
authors.lastname: Dunzendorfer
authors.forename: Romuald
authors.initials: R
authors.lastname: Bellmann
mesh_terms: D000368:Aged; D000418:Albumins / Q000627:therapeutic use*; D000666:Amphotericin B / Q000097:blood* / Q000378:metabolism* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000097:blood* / Q000378:metabolism* / Q000627:therapeutic use; D016638:Critical Illness; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D017093:Liver Failure / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control; D006435:Renal Dialysis
chemical_list: D000418:Albumins; D000935:Antifungal Agents; D000666:Amphotericin B