AMPHOTERICIN-B LIPID COMPLEX

OBJECTIVE: To evaluate the published data on the effectiveness and saf ety of amphotericin B lipid complex (ABLC) for the treatment of invasi ve mycosis and to evaluate data describing the pharmacologic propertie s and pharmacokinetic behavior of ABLC in both animals and humans. DAT A SOURCE: A MEDLINE search was conducted to identify literature publis hed from 1965 to January 1997 for amphotericin B deoxycholate (DCAB) a nd ABLC. In addition, preliminary data published as abstracts and pres ented al national conferences on infectious disease and hematology wit hin the last 6 years were also included in this review. STUDY SELECTIO N: Both human and animal studies were reviewed. Animal and in vitro st udies were selected to evaluate the pharmacologic and toxicologic prop erties of ABLC. For the evaluation of the efficacy, safety, and pharma cokinetic behavior of ABLC, large, well-controlled studies were review ed, In addition, data from open-label and emergency use protocols were also included in the review, DATA EXTRACTION: The study and analytica l methods, results, and conclusions of the selected studies were evalu ated. Pharmacokinetic data for both ABLC and DCAB that were derived fr om human subjects were also evaluated. DATA SYNTHESIS: DCAB has been t he cornerstone for the treatment of invasive mycosis, even though it h as a narrow therapeutic index Infusion-related toxicities (e.g., fever , chills. rigors) are likely due to DCAB stimulation of cytokine and p rostaglandin synthesis, Conversely, nephrotoxicity, the primary non-in fusion-related toxicity, likely results from the nonselective cytotoxi c interaction between DCAB and cholesterol-containing mammalian cells, ABLC represents a new approach to improving the therapeutic index of DCAB. Mammalian cytotoxicity is attenuated by complexing amphotericin B to a mixture of phospholipids. This alters the affinity of amphoteri cin B and decreases its selective transfer from the complex to cholest erol-containing mammalian cells, Fungi also possess Lipase, which impr oves the selective transfer from the complex to ergosterol-containing cell membranes, In humans, the lipid formulation increases the volume of distribution of amphotericin B. Thus, compared with DCAB, larger do ses of ABLC can be administered for a longer duration with less nephro toxicity. However, the prevalence of infusion-related toxicities assoc iated with ABLC is similar to that of DCAB, Whether the alteration in distribution improves efficacy by improving tissue concentrations of a mphotericin B has not been determined. The cost of this agent will lim it its use. CONCLUSIONS: ABLC has been shown to be at least as effecti ve as DCAB, and it has been well tolerated in the clinical studies to date. Despite large dosages and extended courses of administration, th ere is little nephrotoxicity associated with its use, However, the cos t of this agent will limit its use to the treatment of refractory myco sis or to cases where DCAB is contraindicated due to significant renal insufficiency.