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The tissue distribution has been studied in rats of both sexes by whole body autoradiogra phy and by dissection of organs after both a single oral and single intravenous administration of radiolabelled salazosulfapyridine (sulfasalazine, SASP). The compound was labelled in two different positions : 14C in the carboxyl group in the salicylic acid part of the molecule and 3H in the sulfonamide part of the molecule making it possible to follow the metabolites after cleavage of the azobridge.The results of these investigations showed that following oral administration, the drug remained mainly in the gastro-intestinal tract. At about 8 hours a certain tissue distribution was noticed for both 14C and 3H. The distribution pattern was very different for the two labellings : the 14C radioactivity was at that time heterogeneously distributed to certain tissues as liver, bone marrow, intestinal mucosa, kidney, lung, connective tissues, ovary, salivary and harderian gland, while the 3H radioactivity was evenly distributed to all tissues including the central nervous system. The radioactivity was almost eliminated from the tissues within 24 hours.Also after i.v. injection high concentration of radioactivity was found in the gastrointestinal tract. Already 5 min after administration 25% of the dose was found in the duodenum and 30% in the liver, indicating an extensive biliary excretion. Beside the gastrointestinal tract the highest radioactive concentrations were found in the liver, connective tissues, lung, kidney, and blood. The radioactivity of 14C labelled SASP decreased more rapidly than that of the 3H. The distribution pattern was roughly the same when comparing males and female rats. In the fetal tissues the 3H radioactivity passed the placental barrier at 4 hours after the injection and was distributed evenly in the fetal tissues, while the 14C radioactivity was only found in the fetal intestines in small amounts.Trace amounts of excreted radioactivity was found in milk. The milk to plasma ratio for 14C was 0.13±0.01 20 min after intravenous administration.The total recovery of excreted radioactivity in male rats at different doses was 73 ?? 89% for 14C and 79 ?? 92% for 3H. 14C radioactivity was mainly found in the faeces while the 3H activ ity was found in about the same amount in faeces and in urine. Female rats had less faecal excretion than males. Only trace amounts of radioactivity were found in the expired air.

yakubutsu dōtai

Pharmacokinetics of Salazosulfapyridine (Sulfasalazine, SASP). (II). Tissue distribution and excretion of SASP in the rat after a single intravenous or oral administration.