SUMMARY A series of experiments has been performed in healthy male volunteers to investigate the disposition of orally administered disodium azodisalicylate, a potentially useful drug for the treatment of ulcerative colitis. The drug was given by mouth in doses of up to 2 g a day for six weeks and there were no adverse effects. Serum concentrations of the intact compound were low and the serum half-time was 4-12.8 days, probably because of a combination of a low clearance rate and a high apparent volume of distribution. Less than 5% of the ingested dose was excreted unchanged in the urine. Circulating concentrations of 5-ASA and N-acetyl-5-ASA were low and 30% of the equivalent daily dose was excreted in the urine, predominantly as N-acetyl-5-ASA. In most subjects more than 30% of the equivalent daily dose of 5-ASA was recovered from the faeces, either as 5-ASA itself or as the acetylated derivative. As 5-ASA has been shown to be the active therapeutic moiety of sulphasalazine, disodium azodisalicylate appears to be suitable for therapeutic trial in ulcerative colitis. Sulphasalazine (salicylazosulphapyridine) is well established as a valuable form of treatment for ulcerative colitis. It is of value in treating an acute attack of the disease1 2 and is especially useful as maintenance therapy for reducfrg the recurrence rate, which is lowered to about otie quarter of that in untreated subjects.34The mode of action of sulphasalazine is unknown but certain important aspects of its metabolism have been established. When taken by mouth (the usual form of administration) most of the drug reaches the colon intact and is there split by the colonic bacteria into sulphapyridine and 5-aminosalicylic acid (5-ASA). Virtually all the sulphapyridine is absorbed and is then excreted in the urine in conjugated form. Some of the 5-ASA is absorbed and is excreted in the urine as N-acetyl-5-ASA. A large proportion of the 5-ASA is excreted in the faeces.5A previous experiment in patients with ulcerative
Bacampicillin (proposed international nonproprietary name), 1′-ethoxycarbonyloxyethyl 6-(
d
-α-aminophenylacetamido)penicillanate, is a new orally well-absorbed penicillin, highly active in vivo due to rapid transformation into ampicillin. The compound is stable in vitro at gastric pH and hydrolyzed slowly to ampicillin at neutral pH but very rapidly in the presence of biological fluids, e.g., tissue homogenates or serum. In vivo the transformation into ampicillin is so rapid that no unchanged compound could be detected in the blood after oral administration of bacampicillin to rats, dogs, and humans. On oral administration to mice, rats, and dogs, bacampicillin was found to be better absorbed than ampicillin, giving higher and earlier peak blood levels of ampicillin. The bioavailability of bacampicillin in rats and dogs was three to four times higher than that of an equimolar amount of ampicillin. On oral administration to rats, bacampicillin was found to give higher levels of ampicillin in organs such as the kidney, liver, and spleen than ampicillin itself. In “tissue cages” in rats, higher transudate levels of antibiotic were found after oral administration of bacampicillin than after ampicillin. On oral treatment of experimentally infected mice, bacampicillin was found to be more active than ampicillin.
The tissue distribution of 3H‐terbutaline. a new β‐stimulaing tagent, was investigated in mice by whole‐body autoradiography as well as by determinations of unchanged and biotransformed terbutaline in serum, lung, heart, and liver.
The radioactivity was localized mainly to the extracellular space and the levels in most tissues were of the same magnitude as that in blood; no uptake and storage of the drug was observed. Neither terbutaline nor its metabolites penetrated the blood‐brain barrier or the placenta barrier. High relative concentrations of unchanged drug were found in the tissues studied, especially in the lung. A low rate of biotransformation is considered to be the cause for this.
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