TABLE 3.
Tissue concentrations of ATV and RTV, after multiple doses of FA-nanoATV/r and native-drug administration at 20 mg/kg in mice (n = 5)
| Tissue | Sample collectiond | Mean concn (ng/g or μg/ga) in tissue ± SEM |
|||
|---|---|---|---|---|---|
| FA-nanoATV | Native ATV | FA-nanoRTV | Native RTV | ||
| Liver | Day 35, special dietb | 1,314.2 ± 121.7 | 219.6 ± 35.1 | 108.9 ± 19.2 | 0.5 ± 0.3 |
| Day 70, biweekly special dietc | 260.1 ± 40.6 | 55.1 ± 11.6 | 6.9 ± 2.3 | 0.5 ± 0.3 | |
| Day 35, normal diet | 87.7 ± 7.3 | 72.3 ± 10.7 | 44.1 ± 4.2 | 13.4 ± 5.8 | |
| Day 70, biweekly normal diet | 49.0 ± 14.5 | 18.2 ± 3.1 | 9.9 ± 3.6 | 6.5 ± 6.5 | |
| Spleen | Day 35, special diet | 62.9 ± 11.2 | 15.2 ± 3.0 | 75 ± 17.6 | 4.2 ± 1.0 |
| Day 70, biweekly special diet | 9.1 ± 0.4 | 4.5 ± 0.5 | 4.3 ± 1.1 | 2.1 ± 0.3 | |
| Day 35, normal diet | 11.6 ± 0.7 | 10.6 ± 0.9 | 33.2 ± 3.1 | 14.4 ± 6.3 | |
| Day 70, biweekly normal diet | 5.8 ± 1.0 | 2.2 ± 0.2 | 5.9 ± 1.4 | 5.3 ± 4.1 | |
| Kidney | Day 35, special diet | 126.5 ± 14.4 | 31.5 ± 2.8 | 103.2 ± 11.5 | 3.7 ± 0.6 |
| Day 70, biweekly special diet | 33.0 ± 4.1 | 11 ± 1.3 | 9.7 ± 3.0 | 3.2 ± 0.9 | |
| Day 35, normal diet | 17.5 ± 1.7 | 23.2 ± 7.3 | 69.4 ± 7.1 | 21.3 ± 7.5 | |
| Day 70, biweekly normal diet | 7.6 ± 0.9 | 5.9 ± 0.5 | 10.8 ± 3.2 | 8.1 ± 6.5 | |
| Lung | Day 35, special diet | 103.2 ± 35.7 | 28 ± 8.8 | 31.3 ± 10.5 | 2.2 ± 1.0 |
| Day 70, biweekly special diet | 21.7 ± 2.7 | 6.9 ± 1.2 | 2.3 ± 0.7 | 0.9 ± 0.2 | |
| Day 35, normal diet | 15.7 ± 2.3 | 13.8 ± 2.2 | 15.9 ± 2.3 | 4.9 ± 2.0 | |
| Day 70, biweekly normal diet | 65.8 ± 47.5 | 3.1 ± 0.4 | 2.4 ± 0.7 | 1.8 ± 1.3 | |
| Lymph node | Day 35, special diet | 36.1 ± 3.5 | 21.8 ± 2.7 | 23.6 ± 7.2 | 4.3 ± 1.5 |
| Day 70, biweekly special diet | 26.0 ± 1.7 | 20.8 ± 11.6 | 1.9 ± 0.7 | 1.2 ± 0.3 | |
| Day 35, normal diet | 17.8 ± 3.6 | 16.6 ± 11.1 | 25.4 ± 8.7 | 9.1 ± 6.4 | |
| Day 70, biweekly normal diet | 21.8 ± 12.9 | 19.5 ± 8.7 | 10 ± 6.3 | 3.1 ± 1.1 | |
| Brain | Day 35, special diet | 2.78 ± 0.75 | 2.15 ± 0.5 | 0.8 ± 0.27 | —e |
| Day 70, biweekly special diet | 1.14 ± 0.26 | — | — | — | |
| Day 35, normal diet | 0.29 ± 0.07 | 0.68 ± | 0.4 ± 0.08 | — | |
| Day 70, biweekly normal diet | — | — | — | — | |
| Site of injection | Day 35, special diet | 1,145.0 ± 127.8 | 454.4 ± 32.7 | 51.0 ± 17.7 | 9.0 ± 0.5 |
| Day 70, biweekly special diet | 345.8 ± 69.4 | 563.3 ± 191.4 | 0.1 ± 0.0 | 11.6 ± 3.4 | |
| Day 35, normal diet | 847.0 ± 278.0 | 286 ± 50.5 | 11.8 ± 5.9 | 5.4 ± 0.7 | |
| Day 70, biweekly normal diet | 918.5 ± 161 | 302.6 ± 123.5 | 6.9 ± 5.9 | 4.8 ± 2.1 | |
Values for site of injection are in micrograms per gram.
Tissue samples were collected on day 35, i.e., 7 days after the last dose in the weekly-dosing group.
Tissue samples were collected on day 70, i.e., 14 days after the last dose in the biweekly-dosing group.
Special diet is the folate-deficient diet.
—, values are less than the limit of quantitation (i.e., 0.5 ng/ml).