7.1.- TOXICOKINETICS 

7.1.1. Plasma levels in beagle dogs

Blood samples were withdrawn from male and female beagle dogs subjected to 4 weeks intravenous doses of 1, 2 and 3 mg/kg of IQB-9302 (see "4 weeks intravenous subacute toxicity in dogs followed by two week recovery." ) On study days 1 and 28, approximately 7 mL of blood was collected from yugular vein of each dog in the 3 treated groups at 0 (pre-dose), 5, 15 , 30, 60 and 90 min and 3 hours post-dose, transferred to EDTA tubes and placed in ice. The plasma was separated within 2 hours after collection and frozen until analyzed by HPLC (see "Validation of a HPLC assay for IQB-9302 concentrations in dog plasma")

Peak plasma levels ranging between 1 mg/mL and  2 mg/mL were observed 5 minutes after inyection after doses of 1, 2 and 3 mg/kg and were dose-dependent. Mean blood levels on day 28 were similar to those observed after first day, so as neither  impairment of IQB-9302 metabolism or  accumulation of the test compounds were evidenced. Plasma levels decreased rapidly and fell below detection levels (50 ng/ml) after 3 hours in most of animals.
 

7.2. PHARMACOKINETICS

7.2.1. Plasma levels after subcutaneous administration of 14-C-IQB-9302 in rats (Preliminary data)

Radioactive IQB-9302 (figure 1) was subcutaneously inyected at 20 mg/kg to male albino rats. Peak plasma concentrations of radioactivity were found at two hours after dose administration and thereafter declined but were still detectable at 24 hours post-dose.
(figure 2)

Distribution, excretion and metabolic studies are currently in progress at Department of Pharmacokinetics and Metabolism (Huntingdon-Life Sciences)