Table 3.
Circulating absolute monocytes in the blood (macrophage precursors) and incidence and severity of liposomal clodronate-related reduction in liver macrophages following liposome treatment.
| Treatment | Parameters | Prior to Pretreatment | Predose | 48 hr post pretreatmenta | 120 hr post pretreatmenta | 192 hr post pretreatmentb |
|---|---|---|---|---|---|---|
| Clodronate Liposomes + G1-ECD (n = 2) | Absolute Monocytes | NA | 0.39 | 0.30 | 1.00 | 1.14 |
| Reduction in Liver Macrophages | NA | NA | NA | NA | Grade 3 | |
| Empty Liposomes + G1-ECD (n = 2) | Absolute Monocytes | NA | 0.13 | 0.20 | 0.18 | 0.16 |
| Reduction in Liver Macrophages | NA | NA | NA | NA | None | |
| Clodronate Liposomes (n = 1) | Absolute Monocytes | 0.67 | NA | 0.22 | 1.03 | 1.62 |
| Reduction in Liver Macrophages | NA | NA | Grade 5 | Grade 4 | Grade 3 | |
| EmptyLiposomes (n = 1) | Absolute Monocytes | 0.37 | NA | 0.29 | 0.21 | 0.32 |
| Reduction in Liver Macrophages | NA | NA | None | None | None |
Reduction in liver macrophages based on microscopic evaluation conducted on biopsy samples collected from males treated with clodronate liposomes and empty liposomes.
Reduction in liver macrophages based on microscopic evaluation conducted on liver samples collected at necropsy from all males in all groups.
Absolute monocyte units = E3/µL
NA = Not Applicable
Grade 5 = Severe = approximately 95% reduction in macrophage numbers from the baseline
Grade 4 = Marked = approximately 70% reduction in macrophage numbers from the baseline
Grade 3 = Moderate = approximately 40% reduction in macrophage numbers from the baseline
None = No reduction in macrophage numbers from the baseline