Biotransformation of D(-)-ephedrine and L(+)-ephedrine in the rabbit, in vivo and in vitro.

Investigations were carried out with radiolabeled D(-)-ephedrine and L(+)-ephedrine to establish whether differences exist in their metabolic fate in the rabbit, in vivo and in vitro. In liver microsomal preparations, a) D(-)-ephedrine was metabolized at a faster rate than L(+)-ephedrine, b) benzoic acid was formed from D(-)ephedrine at a rate about three times greater than from the L(+)-isomer, and c) the relative amounts of norephedrine and 1-phenyl-1,2-propranediol formed from both ephedrine isomers were nearly identical throughout the entire incubation period. In vivo, both ephedrine isomers were extensively metabolized and the majority of total radioactivity (71-91%) was excreted within 24 hr. A greater 14C-excretion rate was observed for L(+)-ephedrine. From an analysis of 0- to 24-hr urine, it was found that a) 47-50% of the urinary 14C was attributable to acidic metabolites (hippuric acid and benzoic acid) from L(+)- and D(-)-ephedrine, b) from 4 to 16% of the total 14C obtained with both isomers was accountable as 1-phenyl-1,2-propanediol, either free or as a glucuronide conjugate, c) no appreciable quantities of sulfate or glucuronide conjugates of p-hydroxylated metabolites of ephedrine or norephedrine was detectable, and d) small amounts (less than 4% of metabolites corresponding to unchanged ephedrine, norephedrine, or 1-hydroxy-1-phenyl-2-propanone were found in urine of animals given either isomer. These experiments indicate that the major pathway for the biotransformation of D(-)-ephedrine and L(+)-ephedrine involves N-demethylation and oxidative deamination of the side chain.