Clinical and clinical pharmacologic studies of 2-amino-1,3,4-thiadiazole (A-TDA:NSC 4728).

A clinical phase I-II evaluation of 2-amino-1,3,4-thiadiazole (A-TDA) administered daily, twice a week, or weekly was undertaken, in which 71 patients were treated with a range of doses from 2 mg/m2 to 200 mg/m2. Pharmacokinetic studies employing high-performance liquid chromatography (HPLC) demonstrated a terminal (beta) serum half-life of 2.19 h. Stomatitis, dermatitis, nausea, vomiting, and lethargy were observed. No significant leukopenia or thrombocytopenia, however, was noted. A-TDA administration led to hyperuricemia, which was adequately controlled with concurrent administration of allopurinol. Antitumor responses included one partial response in a patient with large cell carcinoma of the lung and three objective responses (2 non-small cell lung and 1 squamous cell carcinoma of the esophagus). Two patients with adenocarcinoma of the lung had a marked improvement of psoriasis during A-TDA therapy. Further phase II studies in patients with cancer and trials in patients with psoriasis are recommended.

Cimetidine and the immune response. I. In vivo augmentation of nonspecific and specific immune response.

Cimetidine is a commonly prescribed histamine antagonist useful in the treatment of peptic ulcer disease. Histamine receptors are found on suppressor T cells and therefore we expected to observe enhanced immune responsiveness in animals treated with this drug. Mice given daily subcutaneous injections of cimetidine (25 or 100 mg/kg) were found to produce approximately twice as much specific antibody in response to tetanus toxoid immunization. Furthermore, mitogen-stimulated splenocytes from cimetidine-treated animals proliferated to a greater extent and produced more immunoglobulin in vitro than controls. These observations offer direct in vivo evidence for immunomodulation by cimetidine.