[Radiochromatography studies on the metabolism of 3H-cyclophosphamide in sheep].

Radiochromatic analyses were made in serum and urine sample fractions as well as in extracts of different organs of a ewe and a ram up to 5 and 14 days, resp., after a single oral dose of 30 mg 3H-cyclophosphamide/kg bodyweight. In a polar and an unpolar system cyclophosphamide (CPM) and up to 7 more hydrophilic and up to 5 more lipophilic metabolites could be characterized by their typical Rf-values. The following results were obtained: 1. At the maximum (1 h p.a.) CPM only showed 25 percent of the total serum concentration and a very short half-life (t 1/2) in the fall of concentration of about 1 h. It was to be analysed up to 48 h. The intensive metabolism was confirmed by a low renal excretion of about 1 percent of the dose. The lipophilic metabolites showed very low concentrations in serum except of 4-keto-CPM, which was analysed over a limited time with higher concentrations but a short half-life; 3 and 8 percent, resp., of dose were excreted in form of this metabolite with urine. 2. 1 or 2, resp., more hydrophilic metabolites with alkylating activity are the chief breakdown products of CPM in sheep. Their part of the total serum concentration falls from 50 percent at the maximum to 25 percent after 24 h. 40 percent of the oral dose were eliminated with urine in form of these metabolites. NH-mustard was found in very low concentration in serum and urine. The course of concentration of these alkylating substances (t 1/2 2 h) corresponds very well with the concentration of the total alkylating activity (NBP-test). 3 mainly hydrophilic metabolites were analysed in all serum and urine samples. 3. More than 90 percent of the residual concentrations found in the organs and tissues after killing the animals were due to alkylating reactions with biologically active metabolites. The analysed more lipophilic breakdown products in the extracts of organs seem to be metabolized to inactive, more hydrophilic substances. CPM was found in smallest concentrations (mug/kg) only in lungs and thymus of the ewe and in kidneys and muscle of the ram. The alkylating main metabolite was questionably analysed only in liver and lung of the ewe. The alkylating reactions reach their maximum at about 2 h p.a. and may be terminated by 48 h p.a.