Pharmacokinetic investigation of ST 789 in rats and mice

Pharmacokinetics of ST 789 were investigated in rats and mice after oral, intravenous, subcutaneous and intramuscular routes. A HPLC method validated for pharmacokinetic studies allowed the Authors to assay ST 789 concentration in plasma, urine and tissues. ST 789 interacted poorly with albumin and plasma proteins. Blood-to-plasma concentration ratio proved to range on average from 1.3 to 2.0 in both in vivo and in vitro studies. Plasma concentration-time behaviour after i.v. injection fitted according to the open three-compartment model; after subcutaneous and intramuscular routes two phases were observed and after oral route the absorption and one elimination phases were detected. Pharmacokinetics of ST 789 proved to vary linearly with the dose administered. Cumulative urinary excretion after parenteral administration ranged on average 60-80% and cumulative biliary excretion was 9.47% of the dose given. Oral administration allowed only 2.5% of the drug given to be excreted in urine, this leading to conclude that this drug is poorly absorbed through the intestine wall. After oral administration ST 789 produced relatively high concentration in lungs and lymphatic tissues, this leading to hypothesize a lymphatic component in its enteral absorption.