Augmentation of Peritoneal Hydraulic Permeability by Amphotericin B: Locus of Action

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Abstract
In normal rabbits, intraperitoneal instillation of amphotericin B increased peritoneal ultrafiltration rates without changing the osmotic gradient. Solute clearances were unaffected. When given intravenously the drug was ineffective, suggesting that amphotericin B acts on the serosal side of the vasculature or mesothelium, presumably creating channels through the membrane, thereby increasing hydraulic permeability. Peritoneal transport rates are much lower than those of hemodialysis (I). To circumvent this deficiency, continuous peritoneal dialysis is now employed in many patients (2). Nevertheless. a segment of patients undergoing continuous ambulatory peritoneal dialysis have, or develop, inadequate transport rates for solutes, or more often for water (3). Hence, their dialyses are not efficient enough for maintenance therapy. It is naive to consider that the peritoileum is inert like hemodialysis membranes. Accordingly, it has been observed that transport rates decrease with systemic vascular disease, or after vasoconstrictor drugs (4, 5) and increase when vasodilators are administered locally or have selective effects on the splanchnic vasculature (5 7). Also small number of studies have demonstrated that drugs, which affect membranes directly modulate peritoneal transport rates (8–10). A preliminary evaluation of the effects of amphotericin B on peritoneal transport rates showed that osmotically induced water flux increases when the drug was given intraperitoneally (11). No direct effect on solute transport was detected and, over the range of 0.5 to 25 mg/kg, we noted no dose effect. Although amphotericin B is so large a solute that its own transmembrane transport would be slow, the site of action could not be determined with confidence from these studies. Accordingly, we undertook to compare the effects of intraperitoneal instillation with those of intravenous administration of amphotericin B in the same experimental animals.