Amphotericin intraperitoneal

Although the intraperitoneal administration of antibiotics offers a convenient and effective treatment alternative for PD-related peritonitis, potential toxicities should be considered. Chemical peritonitis is a potential toxicity associated with IP vancomycin therapy. A series of early reports of chemical peritonitis with vancomycin snggested that the problem may be brand-specific or associated with large doses (1 to 2 g). One prospective study suggested the incidence may be as high as 23% with IP doses of 1 g or more. There may be a hypersensitivity component to the effect, yet patients exhibiting chemical peritonitis have received subsequent doses without adverse effects. The exact etiology of vancomycin-associated chemical peritonitis remains to be clarified. IP amphotericin B also causes pain and chemical peritonitis. However, since IV amphotericin B poorly penetrates into the peritoneal cavity the therapeutic options are limited. ... 

Polyene antibiotics which possess a free amino group, e.g. amphotericin B, react with carbohydrates or their derivatives under appropriate conditions, yielding A -glycosyl derivatives. These derivatives formed water-soluble salts. The N-glucosyl and -glucuronyl derivatives showed similar antifungal activity to the parent compound but reduced systemic toxicity [398,399] and proved effective when administered intraperitoneally in the treatment of experimental candidiasis in mice [400]. 

Chemical modification may considerably reduce the toxicity of polyenes. Amphotericin B methyl, ethyl, propyl or butyl esters have been shown to have LDso values ten times greater than that of the parent compound when intravenously injected into mice [396]. Similarly, the methyl to butyl esters of candi-cidin exhibited LD o values ten to forty times greater than that of candicidin when injected by the intraperitoneal route into mice [396]. 

Figure 5 Renal recovery of A./umigatus WM-1. Mice were challenged intravenously with 1 x 10 conidia and then treated intraperitoneally twice daily for 4 days with LY303366 or with amphotericin at 0, 4, 24. and 48 hr after inoculation of conidia, The levels of amphotericin used are approximately the same (1 mg/kg) or 10 times (10 mg/kg) the dose used in humans.

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