Trial and error: should pregnant women be research subjects?

A single dose of 200 mg/kg razoxane protected mice against the sub-chronic lethal effects (i.e. within 21 days) of 10 mg/kg daunomycin. When the razoxane dose was split into 2 doses of 100 mg/kg, even better protection against higher doses of daunomycin was obtained. The best protective effect was seen when the razoxane was given 24 h before or simultaneously with the daunomycin, and it was still present, though less, 24 h later. Histopathological examination to determine the site of protection showed it to be in the small bowel. Marrow and cardiac tissue showed no evident changes when examined by light microscopy. IT HAS BEEN DEMONSTRATED in a series of experiments (Herman et al., 1974, 1979) that the toxicity of the anthracycline daunomycin (DM) can be greatly reduced by the administration of razoxane (RZ, ICRF-159). Others (Woodman et al., 1975) have found that not only will RZ reduce the toxicity of DM, but it will also enhance its antitumour activity. The mechanism whereby this distinct improvement in the therapeutic ratio of DM is obtained remains unclear, and it seemed of some interest therefore to define it more accurately.