BACKGROUND: The purpose of this study was to evaluate the biodistribution and toxicity of amphotericin B (AmB) following multiple oral administrations of a novel tropically stable lipid-based formulation (iCo-010). METHODS: BALB/c mice were allocated into six groups: oral iCo-010 twice daily for 5 days in the dose of 20, 10, 5 and 2.5 mg/kg; vehicle control; and intravenous boluses of Fungizone 2 mg/kg once daily for 5 days. The animals were sacrificed 12 h following the last administration and blood and tissues were collected. RESULTS: The plasma concentrations of AmB were similar to previously reported after administration of iCo-009. Somewhat lower concentrations of AmB were detected in reticulo-endothelial system in the case of iCo-010 when compared with iCo-009. The concentration in kidney was higher with iCo-010 than with iCo-009. The creatinine levels in all oral treatment groups were in a normal range as in the case of iCo-009. Administration of Fungizone resulted in elevated plasma creatinine levels. Histopathology analysis detected no GI, liver or kidney toxicity following multiple dose oral administration of iCo-010. Fungizone treatment induced necrotic changes in hepatic and kidney tissues. CONCLUSIONS: Given the tropical stability of iCo-010, near identical activity against visceral leishmaniasis and significant concentrations in target organs this formulation has a potential to become a treatment of choice in tropical developing countries.
BACKGROUND: The purpose of this study was to evaluate the biodistribution and toxicity of amphotericin B (AmB) following multiple oral administrations of a novel tropically stable lipid-based formulation (iCo-010). METHODS: BALB/c mice were allocated into six groups: oral iCo-010 twice daily for 5 days in the dose of 20, 10, 5 and 2.5 mg/kg; vehicle control; and intravenous boluses of Fungizone 2 mg/kg once daily for 5 days. The animals were sacrificed 12 h following the last administration and blood and tissues were collected. RESULTS: The plasma concentrations of AmB were similar to previously reported after administration of iCo-009. Somewhat lower concentrations of AmB were detected in reticulo-endothelial system in the case of iCo-010 when compared with iCo-009. The concentration in kidney was higher with iCo-010 than with iCo-009. The creatinine levels in all oral treatment groups were in a normal range as in the case of iCo-009. Administration of Fungizone resulted in elevated plasma creatinine levels. Histopathology analysis detected no GI, liver or kidney toxicity following multiple dose oral administration of iCo-010. Fungizone treatment induced necrotic changes in hepatic and kidney tissues. CONCLUSIONS: Given the tropical stability of iCo-010, near identical activity against visceral leishmaniasis and significant concentrations in target organs this formulation has a potential to become a treatment of choice in tropical developing countries.
Authors: Ellen K Wasan; Karen Bartlett; Pavel Gershkovich; Olena Sivak; Brian Banno; Zhao Wong; Jeffrey Gagnon; Byron Gates; Carlos G Leon; Kishor M Wasan Journal: Int J Pharm Date: 2009-01-17 Impact factor: 5.875
Authors: Pavel Gershkovich; Ellen K Wasan; Molly Lin; Olena Sivak; Carlos G Leon; John G Clement; Kishor M Wasan Journal: J Antimicrob Chemother Date: 2009-04-27 Impact factor: 5.790
Authors: Kishor M Wasan; Ellen K Wasan; Pavel Gershkovich; Xiaohua Zhu; Richard R Tidwell; Karl A Werbovetz; John G Clement; Sheila J Thornton Journal: J Infect Dis Date: 2009-08-01 Impact factor: 5.226
Authors: Mahasen A Radwan; Bushra T AlQuadeib; Lidija Šiller; Matthew C Wright; Benjamin Horrocks Journal: Drug Deliv Date: 2017-11 Impact factor: 6.419