The metabolism and effect on biliary lipids of a new bile acid analog, 7-methyl-deoxycholic acid, were studied and compared with those of deoxycholic acid in the hamster. 14C-Labeled 7-methyl-deoxycholic acid and demycholic acid were adminiete red intravenously or intraduodenally to bile fretula hamssere at 1.0 or 4.0 ~molas per min-kg, and hepatic bile was analyzed for radioactive metabolites and biliary lipid outputs. Deoxycholic acid and 7-methyl-deoxycholic acid were emciently abeorbed from the inwine, extracted by the liver and excreted into bile as taurine and glycine conjugam. Twenty per cent of deoxycholic acid was 7ahydroxylated to cholic acid while 7-methyl-deoxycholic acid did not undergo hydroxylation. During deoxycholic acid inihsion, the biliary secretion of phoepholipid did not increase, and the bile became more lithogenic. In cuntramt, 7-methyl-deoxycholic acid stimulated phoephdpid secretion, and bile became less lithogenic. Although pathologic changes in the liver were inconstant and m d y mild, both bile acids were toxic in the hamster; hemolysis and death due to respiratory distress were observed.
Recent work in this laboratory has dealt with the synthesis of a new series of bile acid analogs. These compounds were identical with the naturally occurring bile acide, but with a methyl substituent as well as a hydroxyl group at carbon-7 (1,2). Such compounds may have cholelitholytic properties since they are similar to the naturally occurring bile acids with respect to hydrophilic-hydrophobic balance. It was hypothesized that the presence of an alkyl group at the 7-position would inhibit or prevent the removal of the 7-hydroxyl subetituent by the intmtinal bacterial flora, thus preserving the analog for prolonged enterohepatic cycling and preventing the formation of potentially toxic secondary bile acids.
Previous studies in the hamster showed that 3a,7adihydroxy-7/3-methyl-5/3-cholanoic acid (7-Me-CDA), 3a,7/3-dihydroxy-7a-methyl-5/3-cholanoic acid (7-Me-