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.
Table 1: Preclinical Toxicity Profile of Orally Administered Stampidine in Small and Large Animal Species.