[Mode of action of chlorambucil. Initial metabolic studies using carbon 14 isotope labeling. Rheumatological implications of their results].
Mode of action of chlorambucil first metabolic studies by means of carbon-14 labelled isotpoes rheumatological implications of the results. Chlorambucil, gamma [rho-di(2-chloroethyl) aminophenyl] butyric acid, was labelled in either the carboxylic group (Ia), the mustard radical (Ib), or the carbon atom in the aplha position in the carboxylic group (Ic). The first studies by total autoradiography of mice, by organ fixation, by analysis of urine, faeces, and  expired air of rats, and by microautoradiography of sections of organs and smears of tissues from rats and rabbits produced the following results: the metabolism of chlorambucil includes a long hepatic time; the molecule undergoes beta-oxidation almost certainly in the liver; thenthe oxidized form become localized in two potential target organs: the thymus and the bone marrow; there is no elective fixation in normal joints of any ot the three labelled compound studied; on the other hand, with all three molecules, there was elimination via the bile ducts, slight movement into the thoracic canal, and labeling ofHarder's glands (particularly with Ia and Ic); elimination of the three compounds in urine was complex. These facts suggest that chlorambucil undergoses activation in the liver, in the same way as cyclophosphamide; however, the similarity end there. The other steps in metabolism give rise to different molecules for these compounds. The high concentrations of chlorambucil in the thymus and the labelling of the marrow cells indicate that the action of this cytostatic compound is primarily immunodepressive.
D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002245:Carbon Dioxide / Q000032:analysis; D002250:Carbon Radioisotopes; D002699:Chlorambucil / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D003864:Depression, Chemical; D005243:Feces / Q000032:analysis; D006243:Harderian Gland / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D051381:Rats; D013950:Thymus Gland / Q000378:metabolism
D002250:Carbon Radioisotopes; D007166:Immunosuppressive Agents; D002245:Carbon Dioxide; D002699:Chlorambucil
Mode d'action du chlorambucil. Premières études métaboliques grâce aux marquages isotopiques par le carbone 14. Implications rhumatologiques de leurs résultats