| |
|
|
|
Highest |
Toxicities Observed |
|
| |
|
|
Daily |
Cumulat. |
|
Toxic |
| |
| Animal |
|
|
Dose |
Dose |
Wt |
|
|
|
|
|
|
PUL |
Organ |
| Species |
N |
Treatment |
mg/kg |
(mg/kg) |
Loss |
HEM |
GI |
LIV |
PA |
RE |
MET |
CV |
Lesions |
| |
|
|
|
|
|
|
|
|
|
|
|
|
|
| Mice |
75 |
po bolus x1 |
25-100 |
100 |
– |
– |
– |
– |
– |
– |
– |
– |
0/22 (N=75) |
| Mice |
165 |
po qd
x 7d-56d |
25-100 |
5,600 |
– |
– |
– |
– |
– |
– |
– |
– |
0/22 (N=105) |
| Rats |
30 |
po qd
x 14d |
25-100 |
1,400 |
– |
– |
– |
– |
– |
– |
– |
– |
0/21 (N=30) |
| Dogs |
9 |
po bid
x 5d-30d |
25-100 |
3,000 |
– |
– |
– |
– |
– |
– |
– |
– |
0/37 (N=5) |
| Cats (AI) |
20 |
po bid
x 28d-49d |
50-100 |
4,900 |
– |
– |
– |
– |
– |
– |
– |
– |
ND |
| Cats (CI)*
Cats (CI) |
10
6 |
po bid
x 28d
po bolus
x 1 |
50-200
50-100 |
5,600
100 |
+
- |
–
- |
+
- |
+
- |
–
- |
–
- |
+
- |
–
- |
0/31 (N=7)
0/31 (N=2) |
Preliminary results were reported in part in reference 34. AI, acutely FIV-infected; CI, chronically FIV-infected; HE, hematologic; G, gastrointestinal; LI, liver; PA, pancreatic;
RE, renal; ME, metabolic; PUL, pulmonary; CV, cardiovascular; See Materials and Methods for experimental details for the toxicity studies presented.
*Three of these cats had two months earlier been treated at either 1.4 g/kg (N=1) or 2.8 g/kg (N=2) dose levels, so that their total cumulative doses were 7.0 g/kg (N=1)
and 8.4 g/kg (N=2), respectively. |