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Articles by C. G Leon
Total Records ( 1 ) for C. G Leon
  P Gershkovich , E. K Wasan , M Lin , O Sivak , C. G Leon , J. G Clement and K. M. Wasan
  Objectives

To assess the pharmacokinetics and biodistribution of amphotericin B (AmB) following oral administration in a novel mono/diglyceride–phospholipid formulation and to compare with intravenous (iv) administrations using commercial formulations.

Methods

Rats were allocated into the following treatment groups: oral gavage of AmB dispersed in mono/diglyceride–phospholipid formulation at doses of 4.5 and 10 mg/kg; iv bolus administration of 0.8 mg/kg Fungizone®; iv bolus of 5 mg/kg Abelcet® and iv bolus of 5 mg/kg AmBisome®. Blood was sampled from jugular vein cannula at certain time points. The animals were sacrificed 72 h following administration of AmB and multiple tissues were harvested. The concentration of AmB in plasma and tissues was determined by means of HPLC. The plasma creatinine concentrations were determined using an enzymatic kit.

Results

The pharmacokinetics and tissue distribution of AmB following iv administrations of the commercial formulations were found to be highly formulation dependent. The terminal half-life and biodistribution of orally administered AmB in a mono/diglyceride–phospholipid formulation resembled those of Fungizone®. The larger volume of the co-administered lipid-based formulation in the case of the higher dose of orally administered AmB resulted in flip-flop kinetics and in preferential distribution into the kidneys. No nephrotoxicity was detected for any formulation and route of administration.

Conclusions

Oral administration of AmB in a mono/diglyceride–phospholipid formulation to rats resulted in significant intestinal absorption into the systemic circulation with pharmacokinetic and biodistribution properties similar to a micellar iv preparation.

 
 
 
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