K Takemoto1, Y Yamamoto, Y Ueda. 1. Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan.
Abstract
BACKGROUND: AmBisome is a small unilamellar vesicle containing amphotericin B. AmBisome is generally unable to pass through the blood-brain barrier, but the distribution of AmBisome in the brain is increased by inflammation, and in consequence, AmBisome exhibits activity against fungal meningitis. We investigated the influence of the progression of cryptococcal meningitis on the brain penetration and efficacy of AmBisome. METHOD: Mice were infected intracerebroventricularly with Cryptococcus neoformans 4 h or 5 days prior to a single dose treatment. RESULTS: The brain tissue level and efficacy of AmBisome when administered 5 days after infection were greater than 4 h after infection. An immunohistochemical study showed that AmBisome-derived amphotericin B was localized at the infected site in the subarachnoid space. When AmBisome was compared with Fungizone at the maximum tolerated dose, 10 mg/kg AmBisome exhibited greater efficacy than 1 mg/kg Fungizone in both regimens. CONCLUSION: The brain penetration of AmBisome was enhanced by the progression of cryptococcal meningitis and correlated with the in vivo activity.
BACKGROUND:AmBisome is a small unilamellar vesicle containing amphotericin B. AmBisome is generally unable to pass through the blood-brain barrier, but the distribution of AmBisome in the brain is increased by inflammation, and in consequence, AmBisome exhibits activity against fungal meningitis. We investigated the influence of the progression of cryptococcal meningitis on the brain penetration and efficacy of AmBisome. METHOD:Mice were infected intracerebroventricularly with Cryptococcus neoformans 4 h or 5 days prior to a single dose treatment. RESULTS: The brain tissue level and efficacy of AmBisome when administered 5 days after infection were greater than 4 h after infection. An immunohistochemical study showed that AmBisome-derived amphotericin B was localized at the infected site in the subarachnoid space. When AmBisome was compared with Fungizone at the maximum tolerated dose, 10 mg/kg AmBisome exhibited greater efficacy than 1 mg/kg Fungizone in both regimens. CONCLUSION: The brain penetration of AmBisome was enhanced by the progression of cryptococcal meningitis and correlated with the in vivo activity.
Authors: Andreas M Grabrucker; Barbara Ruozi; Daniela Belletti; Francesca Pederzoli; Flavio Forni; Maria Angela Vandelli; Giovanni Tosi Journal: Tissue Barriers Date: 2016-02-25
Authors: Hsin-Yun Sun; Barbara D Alexander; Olivier Lortholary; Francoise Dromer; Graeme N Forrest; G Marshall Lyon; Jyoti Somani; Krishan L Gupta; Ramon del Busto; Timothy L Pruett; Costi D Sifri; Ajit P Limaye; George T John; Goran B Klintmalm; Kenneth Pursell; Valentina Stosor; Michelle I Morris; Lorraine A Dowdy; Patricia Munoz; Andre C Kalil; Julia Garcia-Diaz; Susan Orloff; Andrew A House; Sally Houston; Dannah Wray; Shirish Huprikar; Leonard B Johnson; Atul Humar; Raymund R Razonable; Shahid Husain; Nina Singh Journal: Clin Infect Dis Date: 2009-12-01 Impact factor: 9.079