The purpose of this present work has been to study the pharmacokinetical profile of E-4441 in the rat, mouse and cynomolgus monkey. Analytical determination of the levels in plasma, urine and organs was affected by two different techniques: a microbiological agar diffusion assay with Bacillus subtilis, and HPLC with preliminary extraction in chloroform (pH 8.5). The kinetic behaviour of the unchanged substance was similar in the three animal species studied. Absorption and excretion took place rapidly (T1/2a = 2-20 min, T1/2el = 25-225 min). In mouse there is a linear relationship between administered dose and the area under the curve (AUC) of plasma levels. The absolute bioavailability of unchanged E-4441 is of 20% and the urinary excretion represents 1 to 2% of the administered oral dose. The organs in which the highest concentrations of substance were found were bile, liver and kidney, while the substance could not be detected in brain, testis, ovary or adipose tissue.
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