Table 3.
Efficacy of Liposomal Amphotericin B and Deoxycholate Amphotericin B at Different Doses in Animal Models of Fungal Infection
| Tissue | Disease Model (Species) | Treatment | Dose (mg/kg) | % Survival | Log 10 Colony-forming Units | Reference |
|---|---|---|---|---|---|---|
| Lung | Aspergillosis (Rabbit) | LAmB | 0,a 1.0, 5.0, 10.0 | 7, 80, 100, 80 | 1.6-, 8-, 15-, 15-fold reduction compared with untreated animals | Francis et al (1994) [150] |
| DAmB | 1.0 | 30 | 15-fold reduction compared with untreated animals | |||
| Aspergillosis (Rat) | LAmB | 0, 1.0, 10.0 | 0, 0, 27 | 2.5, 0.9, 1.1 | Leenders et al (1996) [159] | |
| DAmB | 1.0 | 13 | 2.0 | |||
| Aspergillosis (Mouse) | LAmB | 0, 15 | 0, 86 | 4.5, 3.2 | Olson et al (2001) [160] | |
| ABLC | 15 | 29 | 4.5 | |||
| Aspergillosis (Mouse) | LAmB | 0, 6.05b | 40, 100 | 5.3, 0.54 | Allen et al (1994) [161] | |
| DAmB | 6.73b | 100 | 3.31 | |||
| Blastomycosis (Mouse) | LAmB | 0, 1.0, 3.0, 7.5, 15 | 0, 90, 100, 100, 100 | ---,c 6.53, 3.42, 0.22, 0.42 | Clemons et al (1993) [156] | |
| DAmB | 1.0 | 10 | 3.46 | |||
| Paracoccidioidomycosis (Mouse) | LAmB | 0, 0.6, 5.0, 15, 30 | 0, 7.1, 80, 79, 67 | ---,c 4.02, 5.09, 1.25, 0.56 | Clemons et al (1993) [157] | |
| DAmB | 0.6 | 47 | 7.11 | |||
| Brain | Coccidioidomycosis (Rabbit) | LAmB | 0, 7.5, 15, 22.5 | 37.5, 100, 100, 100 | 3.11, 1.18, 0.46, 1.11 | Clemons et al (2002) [162] |
| DAmB | 1.0 | 100 | 2.06 | |||
| Cryptococcosis (Mouse) | LAmB | 0, 3, 20, 30 | 0, 100, 100, 100 | 8.89, 5.96, 1.11, 0.61 | Albert et al (1995) [163] | |
| DAmB | 3.0 (intraperitoneal dosing) | 89 | 8.79 | |||
| Kidney | Candidiasis (Mouse) | LAmB | 0, 0.3, 7.0 | 10, 50, 100 | ---,c 3.96, 0.39 | Van Etten et al (1993) [155] |
| DAmB | 0.3 | 100 | 5.28 | |||
| Candidiasis (Rabbit) | LAmB | 0, 5.0 | 100, 100 | Significantly reduced (P < .01)d | Groll et al (2001) [164] | |
| DAmB | 1.0 | 100 | Significantly reduced (P < .001)d | |||
| ABLC | 5.0 | 100 | Not significantd | |||
| ABCD | 5.0 | 100 | Not significantd | |||
| Candidiasis (Mouse) | LAmB | 0, 1.0,e 5.0, 20.0 | 100, 100, 100, 100 | 6.22, 3.22, 3.46, 2.67 | Garcia et al (2000) [143] | |
| DAmB | 1.0 | 100 | 4.18 | |||
| Liver | Leishmaniasis | LAmB | 0, 0.04, 0.2, 1.0, 5.0 | 100, 100, 100, 100, 100 | 0, 15.8,f 41.2, 84.5, 99.8 | Croft et al (1991) [165] |
| DAmB | 0.04, 0.2, 1.0 | 100, 100, 100 | 3.4,f 22.0, 52.7 | |||
| Leishmaniasis | LAmB | 0, 0.8, 5.0, 50.0 | 100, 96, 96, 100 | 6.0, 1.0, 0, 0 | Gangneux et al (1996) [137] | |
| DAmB | 0.8 | 92 | 4.0 | |||
| Fusariosis | LAmB | 0, 3.0, 5.0, 10.0, 20.0 | 50, 100, 100, 100 | 4.8, 2.5, 2.7, 2.3, 2.4 | Ortoneda et al (2002) [166] | |
| DAmB | 1.5, 2.5 | 60, 100 | 4.2, 3.9 | |||
| Spleen | Histoplasmosis | LAmB | 0, 0.3, 0.6, 6.0 | 100, 100, 100, 100 | 8.68, 7.20, 6.66, 3.89 | Adler-Moore (1994) [35] |
| DAmB | 0.3, 0.6 | 100, 100 | 7.34, 6.30 | |||
| Leishmaniasis | LAmB | 0, 0.8, 5.0, 50.0 | 100, 96, 96, 100 | 7.0, 3.0, 0, 0 | Gangneux et al (1996) [137] | |
| DAmB | 0.8 | 92 | 6.5 | |||
| Fusariosis | LAmB | 0, 3.0, 5.0, 10, 20 | 50, 100, 100, 100 | 5.7, 4.5, 4.5, 3.2, 3.3 | Ortoneda et al (2002) [166] | |
| DAmB | 1.5, 2.5 | 60, 100 | 5.4, 5.3 | |||
| Mucosa | Vaginal candidiasis (Mouse) | LAmB | 0, 15, 20 | 100, 100, 100 |
3.26, 0, 0 (vaginal tissue) 3.0, 0, 0 (lavage) |
Gibbs et al (2002) [167] |
| Skin | Leishmaniasis | LAmB | 0, 6.25, 12.5, 25, 50 | 100, 100, 100, 100, 100 | +90,g +92, +45, –8, –68 | Yardley et al (1997) [168] |
| DAmB | 0.5 | 100 | +72g |
Adapted from Adler-Moore J and Proffit RT. Curr Opin Investig Drugs 2003; 4:179–85 [158].
a0 represents untreated control group throughout entire table.
bTotal dose as aerosol prophylaxis.
cColony-formimng units (CFUs) could not be determined, as all mice died by CFU assessment time.
dReductions in CFU compared with controls for significance.
eSingle-dose prophylaxis.
fPercentage clearance or inhibition of amastigotes in the liver.
gPercentage change in lesion size on day 24 post-treatment.
Abbreviations: ABCD, amphotericin B colloidal dispersion; ABLC, amphotericin B lipid complex; DAmB, deoxycholate amphotericin B; LAmB, liposomal amphotericin B.