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

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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.