Variability in polyene content and cellular toxicity among deoxycholate amphotericin B formulations.
OBJECTIVE
To evaluate the toxicity of amphotericin B deoxycholate formulations.


METHODS
In vitro experiment.


METHODS
University research center.


METHODS
Human mononuclear THP-1 cells.


METHODS
The human mononuclear cells were exposed in vitro for 2 hours to the following deoxycholate formulations of amphotericin B, in 2.5- and 5-micro/ml concentrations: Apothecon, Pharmacia, Sigma, Gensia, Pharma-Tek, and VHA.


RESULTS
Toxicity of the amphotericin B formulations were assessed by measuring interleukin (IL)-1beta expression in an in vitro model. Amphotericin B content was measured by enzyme-linked immunosorbent assay (ELISA), and amphotericin A and B contents were assessed by spectrophotometry. Endotoxin contamination was evaluated in all reagents. Expression of IL-1beta from Sigma, Pharmacia, and Pharma-Tek formulations was increased approximately 250%, 50%, and 25%, respectively, compared with amphotericin A. Amphotericin B content of Sigma, Pharmacia, Pharma-Tek, and Gensia formulations, as measured by ELISA, was increased approximately 450%, 200%, 200%, and 100%, respectively, compared with Apothecon. This variation could not be explained by differences in amphotericin A or B content as measured by spectrophotometry.


CONCLUSIONS
Amphotericin B is obtained from a fermentation plant and manufactured as a pharmaceutical at different facilities. Both previous clinical observations and the current in vitro evaluation revealed significant differences among the formulations. Likely, other polyenes or pyrogenic toxins in differing amounts are in these formulations, thus explaining the variability in toxicity observed among the formulations.
Cleary
John D
JD
Department of Clinical Pharmacy, University of Mississippi School of Pharmacy, Jackson 39216, USA. jcleary@medicine.umsmed.edu
Rogers
P David
PD
Chapman
Stanley W
SW
D000666:Amphotericin B / Q000032:analysis* / Q000633:toxicity; D000935:Antifungal Agents / Q000032:analysis* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003840:Deoxycholic Acid / Q000031:analogs & derivatives* / Q000032:analysis* / Q000633:toxicity; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis; D009000:Monocytes; D011090:Polyenes / Q000032:analysis*; D013053:Spectrophotometry
D000935:Antifungal Agents; D004338:Drug Combinations; D007375:Interleukin-1; D011090:Polyenes; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination