Abstract
Summary
The distribution and excretion of atabrine is similar in the rat and dog. The highest concentrations of the drug were found in the liver. These concentrations were not diminished 3 days after the administration of the drug and although the concentrations were diminished after 8 days, appreciable concentrations were found in the livers as late as 2 weeks after the administration of single or multiple doses of the drug. Intermediate concentrations were found in the spleen and kidney. These concentrations were not significantly diminished 2 weeks after administration of the drug was ceased. Intermediate concentrations of the drug were found in bone marrow and the wall of the small intestine. All other tissues studied showed low concentrations of the drug.
The elimination of the drug is slow. The urinary concentration of the drug never reaches high values, nor does the total output per day reflect the size of the dose administered. Large amounts of the drug are excreted by way of the bowel, and this mode of excretion continues long after the administration of the drug has been discontinued.
Following oral or intravenous administration of atabrine the concentration of the drug in the blood stream remains very low, never exceeding 1 mg % even after the administration of large multiple doses, but these low concentrations are maintained for days after administration of the drug is stopped. The blood concentration bears no apparent relationship to the dose administered. These results together with findings on the distribution and excretion of the drug, suggest that the drug is deposited in the tissues and is slowly liberated, thereby maintaining a rather constant blood concentration of the drug.
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