title: Effect of variation in infusion time and macrophage blockade on organ uptake of amphotericin B-deoxycholate.
abstract: Amphotericin B is administered as a colloidal suspension due to its insolubility in water. Macrophages, particularly those in the liver, have been implicated as the predominant cell type responsible for the uptake of colloidal amphotericin B. We examined the effect of infusion time and macrophage function to confirm the role of the macrophage in the uptake of amphotericin B. Prolonged infusion time (24 h compared to 6 h) resulted in significantly less hepatic and splenic accumulation of amphotericin B. Blockade of macrophage function with methylpalmitate also resulted in significantly decreased hepatic and splenic uptake of amphotericin B. Uptake of amphotericin B by lung macrophages was not significantly affected by methylpalmitate. The area under the serum concentration versus time curve was significantly higher in the group that received methylpalmitate compared to either the 6 or 24 h amphotericin B infusion groups. These results suggest that fixed macrophages play an important part in the pharmacokinetics of amphotericin B, and that increasing drug solubility may alter the pharmacokinetics of amphotericin B.
authors.affiliation: Department of Medicine, Mary Imogene Bassett Hospital, Cooperstown, New York 13326.
authors.forename: L C
authors.initials: LC
authors.lastname: Edmonds
authors.forename: L
authors.initials: L
authors.lastname: Davidson
authors.forename: J S
authors.initials: JS
authors.lastname: Bertino
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D003102:Colloids; D003840:Deoxycholic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D011817:Rabbits; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D003102:Colloids; D004338:Drug Combinations; D010168:Palmitates; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination; C019012:methyl palmitate