Pharmacokinetic parameters for mice receiving i.v. SL-DXR at a dose of 9 mg/kg q1 week, q2 weeks, or q4 weeks The AUC values were calculated using the trapezoidal rule. Plasma and tissue t1/2 values were calculated using the formula t1/2 = 0.693/kelm, where kelm is the elimination constant derived from the plasma or tissue concentration versus time curve.
Dose | Plasma | Skin | Paws | ||||||
|---|---|---|---|---|---|---|---|---|---|
| t1/2 |
AUC
| t1/2 |
AUC
| t1/2 |
AUC
| ||||
| h | doxorubicin μEq × h/ml | h | doxorubicin μEq × h/g | h | doxorubicin μEq × h/g | ||||
| 9 mg/kg q1 week | |||||||||
| 1 | 39.4 | 9,141.0 | N.D. | 589.0 | N.D. | 1,473.0 | |||
| 2 | 43.0 | 14,648.0 | N.D. | 1,010.0 | N.D. | 1,446.0 | |||
| 3 | 43.0 | 12,628.0 | N.D. | 1,680.0 | N.D. | 1,549.0 | |||
| 4 | 44.7 | 12,249.0 | N.D. | 1,592.0 | N.D. | 1,475.0 | |||
| C ss | n/a | 72.9 | n/a | 9.48 | n/a | 8.78 | |||
| 9 mg/kg q2 weeks | |||||||||
| 1 | 28.6 | 9,267.0 | 58.2 | 865.0 | 81.5 | 2,308.0 | |||
| 2 | 35.2 | 12,359.0 | 37.9 | 1,283.0 | 100.0 | 2,071.0 | |||
| 3 | 41.5 | 12,450.0 | 139.0 | 1,792.0 | 157.0 | 1,454.0 | |||
| 4 | 44.4 | 12,302.0 | 218.0 | 1,964.0 | 178.0 | 1,384.0 | |||
| C ss | n/a | 33.2 | n/a | 5.84 | n/a | 4.11 | |||
| 9 mg/kg q4 weeks | |||||||||
| 1 | 41.5 | 9,813.0 | 136.0 | 800.0 | 103.0 | 3,213.0 | |||
| 2 | 33.2 | 9,962.0 | 103.0 | 1,136.0 | 147.0 | 1,717.0 | |||
| 3 | 31.6 | 11,019.0 | 147.0 | 1,337.0 | 198.0 | 1,465.0 | |||
| 4 | 46.8 | 10,727.0 | 105.0 | 1,595.0 | 192.0 | 1,645.0 | |||
|
C
ss
|
n/a
|
14.6
|
n/a
|
2.37
|
n/a
|
2.45
| |||
N.D., not determined; n/a, not applicable.