Drug Concentrations in Urine Following Single, Multiple or Intermittent Treatment with Increasing Doses of Liposomal Amphotericin B (LAmB) Versus Amphotericin B (amp)

Ref ID: 18804

Author:

N. Nguyen, BS – Res Assist, J. A. Olson, MS – Scientist, J. Ruiz, BS – Res Assist, J. Adler-Moore, PhD – Professor;

Author address:

Cal Poly Univ, Pomona, CA.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: Azoles and echinocandins are often used to treat urinary tract yeast infections in hospitalized patients, but when there is drug resistance, LAmB with its reduced toxicity may be an option. Because there is limited LAmB pharmacokinetics for the urine, we examined the urine versus kidney and spleen drug concentrations over time in LAmB and amp treated mice. Methods: Mice (n = 7/gp) were given i.v. single, multiple daily or intermittent (d0,3 or d0, d2, d4) doses of 5 or 15mg/kg LAmB (AmBisome63720;) or 0.75 mg/kg amp, with urine and tissue samples collected at 24h, 96h, 168h post-treatment. Tissue samples were homogenized, and all samples were diluted with methanol, heated at 65°C for 10 min., centrifuged and supernatants tested for drug levels using an Agar Bioassay with Candida albicans as the indicator yeast (lower limit detection = 0.25ug/ml). Results: Urine drug levels were significantly higher (p 8804; 0.005) with 6X daily dosing with 15mg/kg LAmB at 24h, 96h, 168h post-treatment (40, 18, 5 ug/ml) vs 1X dosing (5, 4, 3 ug/ml). In contrast, dosing with 5mg/kg 6X, 1X or intermittently yielded urine drug levels that remained between 2-5ug/ml at all timepoints. With 0.75mg/kg amp, significantly higher urine levels (p 8804; 0.003) were seen with 6X vs 1X dosing at 24h post-treatment (8ug/ml vs 2 ug/ml), but unlike LAmB, there was no detectable amp in urine by 96h. In the kidneys and spleen significantly higher LAmB levels (p 8804; 0.05) were seen with 6X vs 1X dosing at 24h and 168h, with drug levels remaining elevated between 24h and 168h following the multiple dosing regimen. Conclusions: Unlike amp, all LAmB dosing regimens (single, daily or intermittent) resulted in urine drug concentrations above the MIC for many Candida spp for up to one week post-treatment indicating that treatment with LAmB can provide sustained antifungal activity for urinary tract yeast infections.

Abstract Number: M-992

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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