P. Murphy, T. Williams, J. K. Smallwood
Jul 24, 1978
Citations
0
Influential Citations
5
Citations
Quality indicators
Journal
Life sciences
Abstract
Abstract The metabolism of drobuline has been examined in the dog, rabbit, rat, guinea pig and hamster. In the dog, unlike the other species, glucuronide conjugation is the major route of metabolism. The structure of the conjugate has been established as an O-glucuronide by isolation using HPLC following by field desorption mass spectral analysis. When the separate d - and l -isomers of drobuline were administered to a series of dogs the l -isomer reached plasma levels approximately three time higher than those of the d -isomer. Deuterium labeled drobuline was synthesized and resolved by multiple crystallizations of the malate salts. Racemic mixtures containing d 6 - d and h 6 - l drobuline and d 6 - l and h 6 - d drobuline were prepared and analyzed by GC-MS as the pentafluoropropionate derivatives. When either racemic mixture was administered to dogs (10 mg/kg, p.o.) the plasma levels of the l -isomer were found to be approximately three times those of the d -isomer. Using these deuterium labeled mixtures the disposition of the two isomers has been examined in the isolated perfused dog liver, in hepatocytes and isolated microsomes. The results indicate that the difference in plasma levels of the d - and l -isomers is not dependent upon stereospecific absorption or excretion but rather it is caused by metabolism of the d -isomer at a faster rate than that of the l -isomer.