Pharmacokinetics of acrylamide after oral administration in male rats

Acrylamide (AMD) is a commonly used industrial chemical. However, it produc es a dying back type of peripheral neuropathy in animals and man. This stud y was performed to investigate the pharmacokinetics of AMD after oral admin istration at 50 mg/g ([1-C-14]AMD) in male Sprague-Dawley rats. Absorption from the gastrointestinal tract was rapid and radioactivity was detected in blood 5 min post-administration, The peak plasma concentration occurred 38 min after administration and was equivalent to 47 mu g/ml. The elimination pattern for plasma was fitted to a one-compartment model with 6 h half-lif e. However, in the blood the elimination pattern was fitted to a two-compar tment model with 7.93 and 374 h for distribution and elimination phases, re spectively. Tissue concentrations of radioactivity determined at 28 and 144 h post-administration differed substantially. After 28 h the highest activ ity was in the gastric content, followed by stomach, lung, bone marrow and skin, while after 144 h the order of total radioactivity was lung > bone ma rrow > esophagus. The activities in the rest of the organs in both experime nts were very low. The excretion study revealed that the kidney is the majo r route of elimination and the majority of radioactivity in urine was excre ted during the first 12 h. The feces contained approximately 10% of the adm inistered dose after 144 h. This study indicated that AMD is rapidly absorb ed from the rat's gastrointestinal tract, distributed and eliminated from t he body. AMD bound but did not accumulate in the erythrocytes or the neural tissues. (C) 1999 Elsevier Science B.V. All rights reserved.