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Role of Phospholipid Transfer Protein on the Plasma Distribution of Amphotericin B Following the Incubation of Different Amphotericin B Formulations

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Purpose

The purpose of this study was to investigate the role of phospholipid transfer protein (PLTP) on the plasma distribution of amphotericin B (AmpB) following incubation with different AmpB formulations in human plasmas with varying lipid profiles.

Methods

In a first set of experiments, plasma distribution profiles of AmpB were determined following the incubation of Fungizone® and lipid-based formulations (Abelcet® and AmBisome®) at a concentration of 20 μg AmpB/mL for 5–120 min at 37°C in the plasma obtained from six different individuals (total cholesterol concentrations range between 62 and 332 mg/dL). In a second set of experiments, Abelcet®, and AmBisome® at a concentration of 20 μg AmpB/mL were incubated for 5 min at 37°C in human plasma (total cholesterol = 163 mg/dL) that had been pretreated with an antibody raised up against PLTP (1:400 v/v dilution from stock solution) for 20 min at 37°C. Following incubation, the human plasma was separated into its lipoprotein and lipoprotein-deficient fractions by density gradient ultracentrifugation and analyzed for AmpB content by high-performance liquid chromatography.

Results

The majority of AmpB was covered in the lipoprotein-deficient plasma and high-density lipoprotein (HDL) fractions following incubation of Fungizone® in human plasma. The majority of AmpB (48.7–87.2%) was recovered in the HDL fraction following incubation of Abelcet® and AmBisome® in human plasma. The presence of the PLTP antibody resulted in a 20% decrease in the percentage AmpB recovered in the HDL fraction following the incubation of Abelcet®. However, the plasma distribution of AmpB remained unchanged following the incubation of AmBisome® in plasma containing the PLTP antibody.

Conclusions

Taken together, these findings suggest indirect evidence that PLTP may play an important role in the plasma distribution profile of AmpB following the incubation of Abelcet® and may be one of the factors responsible for the preferential association of AmpB with HDL when administered as Abelcet®.

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Acknowledgment

This work was supported with an operating grant from the Canadian Institutes of Health Research (grant #MOP-77541 to Dr. Kishor M. Wasan).

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Authors and Affiliations

  1. Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, British Columbia, V6T 1Z3, Canada

    Nilesh Patankar & Kishor M. Wasan

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  1. Nilesh Patankar
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  2. Kishor M. Wasan
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Correspondence to Kishor M. Wasan.

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Patankar, N., Wasan, K.M. Role of Phospholipid Transfer Protein on the Plasma Distribution of Amphotericin B Following the Incubation of Different Amphotericin B Formulations. Pharm Res 23, 1020–1024 (2006). https://doi.org/10.1007/s11095-006-9900-x

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  • DOI: https://doi.org/10.1007/s11095-006-9900-x

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