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1. アムホテシリンBによる腎毒性 amphotericin b nephrotoxicity

English Journal

Preparation and characterization of amorphous amphotericin B nanoparticles for oral administration through liquid antisolvent precipitation.

Zu Y1, Sun W1, Zhao X2, Wang W1, Li Y1, Ge Y1, Liu Y1, Wang K1.Author information 1Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, Heilongjiang, China.2Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Ministry of Education, Harbin 150040, Heilongjiang, China. Electronic address: xiuhuazhao@nefu.edu.cn.AbstractWe prepared amphotericin B (AmB) nanoparticles through liquid antisolvent precipitation (LAP) and by freeze-drying to improve the solubility of AmB for oral administration. The LAP was optimized through a single-factor experiment. We determined the effects of surfactants and their concentration, the stirring time, the precipitation temperature, the stirring intensity, the drug concentration and the volume ratio of antisolvent to solvent on the mean particle size (MPS) of the AmB nanoparticles. Increased stirring intensity and precipitation time favored AmB nanoparticles with smaller MPS, but precipitation times exceeding 30min did not further reduce the MPS. Increased Tween-80 concentration and the drug concentration decreased the MPS of the AmB nanoparticles. Increased precipitation temperature and antisolvent to solvent volume ratio initially decreased the MPS of the AmB nanoparticles, which increased thereafter. Optimum conditions produced AmB nanoparticles with an MPS of 135.1nm. The AmB nanoparticles were characterized through scanning electron microscopy (SEM), mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TG), solvent residue, drug purity test, and dissolution testing. The analyses indicated that the chemical structure of AmB remained unchanged in the nanoparticles, but the structure was changed from crystalline to amorphous. The residual DMSO in the nanoparticles was 0.24% less than the standard set by the International Conference on Harmonization limit for class III solvents. The AmB nanoparticles exhibited 2.1 times faster dissolution rates and 13 times equilibrium solubility compared with the raw drug. The detection results indicate that the AmB nanoparticles potentially improved the oral absorption of AmB.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.Eur J Pharm Sci.2014 Mar 12;53:109-17. doi: 10.1016/j.ejps.2013.12.005. Epub 2013 Dec 15.
We prepared amphotericin B (AmB) nanoparticles through liquid antisolvent precipitation (LAP) and by freeze-drying to improve the solubility of AmB for oral administration. The LAP was optimized through a single-factor experiment. We determined the effects of surfactants and their concentration, the
PMID 24345795

In Vitro Synergistic Effect of Amphotericin B and Allicin on Leishmania donovani and L. infantum.

Corral MJ1, González-Sánchez E, Cuquerella M, Alunda JM.Author information 1Department of Animal Health, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, Madrid, Spain.AbstractCurrent monotherapy against visceral leishmaniasis has serious side effects, and resistant Leishmania strains have been identified. Amphotericin B (AmB) has shown an extraordinary antileishmanial efficacy without emergence of resistance; however, toxicity has limited its general use. Results obtained showed, using a fixed-ratio analysis, that the combination of diallyl thiosulfinate (allicin) and AmB ranged from moderately synergic to synergic at low concentrations (0.07 μM AmB plus 35.45 μM allicin induced 95% growth inhibition). None of the treatments, alone or in combination, had noticeable adverse effects on macrophages (M) in the concentration range examined (allicin, 0.5, 1, 5 and 10 μM; AmB, 0.05, 0.075, and 0.1 μM). Allicin, AmB, or the combination did not affect the infection rate (percentage of infected M) of Leishmania. Allicin enhanced the activity of AmB on intracellular amastigotes of Leishmania donovani and L. infantum (ca. 45% reduction of amastigote burden with 0.05 μM AmB plus 10 μM allicin); this represented nearly a 2-fold reduction in the 50% inhibitory concentration (IC50) of the antibiotic added alone. Results point toward the possible utility of testing this combination in vivo to reduce the toxicity associated with monotherapy with AmB.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2014 Mar;58(3):1596-602. doi: 10.1128/AAC.00710-13. Epub 2013 Dec 23.
Current monotherapy against visceral leishmaniasis has serious side effects, and resistant Leishmania strains have been identified. Amphotericin B (AmB) has shown an extraordinary antileishmanial efficacy without emergence of resistance; however, toxicity has limited its general use. Results obtaine
PMID 24366748

Molecular identification and antifungal susceptibility of yeast isolates causing fungemia collected in a population-based study in Spain in 2010 and 2011.

Guinea J1, Zaragoza O, Escribano P, Martín-Mazuelos E, Pemán J, Sánchez-Reus F, Cuenca-Estrella M; CANDIPOP Project, GEIH-GEMICOMED (SEIMC), and REIPI.Author information 1Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain.AbstractWe report the molecular identifications and antifungal susceptibilities of the isolates causing fungemia collected in the CANDIPOP population-based study conducted in 29 Spanish hospitals. A total of 781 isolates (from 767 patients, 14 of them having mixed fungemia) were collected. The species found most frequently were Candida albicans (44.6%), Candida parapsilosis (24.5%), Candida glabrata (13.2%), Candida tropicalis (7.6%), Candida krusei (1.9%), Candida guilliermondii (1.7%), and Candida lusitaniae (1.3%). Other Candida and non-Candida species accounted for approximately 5% of the isolates. The presence of cryptic species was low. Compared to findings of previous studies conducted in Spain, the frequency of C. glabrata has increased. Antifungal susceptibility testing was performed by using EUCAST and CLSI M27-A3 reference procedures; the two methods were comparable. The rate of fluconazole-susceptible isolates was 80%, which appears to be a decrease compared to findings of previous studies, explained mainly by the higher frequency of C. glabrata. Using the species-specific breakpoints and epidemiological cutoff values, the rate of voriconazole and posaconazole in vitro resistance was low (<2%). In the case of C. tropicalis, using the EUCAST procedure, the rate of azole resistance was around 20%. There was a correlation between the previous use of azoles and the presence of fluconazole-resistant isolates. Resistance to echinocandins was very rare (2%), and resistance to amphotericin B also was very uncommon. The sequencing of the hot spot (HS) regions from FKS1 or FKS2 genes in echinocandin-resistant isolates revealed previously described point mutations. The decrease in the susceptibility to fluconazole in Spanish isolates should be closely monitored in future studies.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2014 Mar;58(3):1529-37. doi: 10.1128/AAC.02155-13. Epub 2013 Dec 23.
We report the molecular identifications and antifungal susceptibilities of the isolates causing fungemia collected in the CANDIPOP population-based study conducted in 29 Spanish hospitals. A total of 781 isolates (from 767 patients, 14 of them having mixed fungemia) were collected. The species found
PMID 24366741

Japanese Journal

Overview of amphotericin B colloidal dispersion(Amphocil)

J Infect 28(suppl I), 45-49, 1994
NAID 30015194899

「アムホテリシンB」

　　[★]

英: amphotericin B, AMPH-B, AMPH
ラ: amphotericinum-B
商: ファンギゾン、ハリゾン、アムビゾーム Ambisome, Amphocil, Amphotec
関: 抗真菌薬、ポリエンマクロライド系抗生物質、アムホテリシンBリポソーム製剤

抗菌薬

ポリエン系

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Amphocil

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