Surprises and omissions in toxicology.
The paper describes expected and unexpected results gained from studies performed decades ago, and so to say - forgotten. 1. Different bacterial toxins can induce considerable changes in pharmacokinetics and pharmacodynamics of applied drugs. To admit clinical trials, only results from healthy human volunteers are required, however. 2. Antagonists to the toxicity of bacterial toxins in general have to be administered prior to the toxin. However, adenosine triphosphate (ATP) is effective also when applied after toxins. ATP is "in" again in contemporary research. 3. A controlled clinical trial revealed substantial differences between the D- and D,L-form of cycloserin. 4. The antimetabolite 6-azauracil riboside and eventually its triacetate derivative was claimed to possess antitumor properties. However, a controlled clinical trial did not confirm its potency in this aspect. On the other hand, the tolerance was excellent. This finding encouraged clinical trials in psoriasis, a disease of autoimmune etiology. Moreover, beneficial effects and tolerance of the compound was described in herpes zoster and even in smallpox. On the basis of these results a controlled clinical trial in rheumatoid arthritis, also judged to be an autoimmune disease, was started. Because of early high toxicity, the study was discontinued. 5. High doses of the compound induce ocular lesions in animals. The above examples justify the titel of this paper.
Rasková
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H
Charles University, Prague, Czech Republic.
Zídek
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D000818:Animals; D018849:Controlled Clinical Trials as Topic; D006801:Humans; D014116:Toxicology / Q000639:trends*