ABSORPTION, METABOLISM AND EXCRETION OF THE EPHEDRINES IN MAN. I. THE INFLUENCE OF URINARY pH AND URINE VOLUME OUTPUT

¹ Department of Pharmacy, Chelsea College of Science and Technology, University of London, London S. W. s, England

The urinary excretion in man of ()-norephedrine, ()-ephedrine and ()-methylephedrine under extreme acidic and alkaline urinary conditions has been studied to determine whether the drugs undergo pH-dependent renal reabsorption, and, if so, what effect this has upon the elimination processes of the drugs. Both urinary excretion and relative metabolism of all the ephedrines are pH-dependent. However, the extent of this dependence, termed pH-sensitivity, varies, increasing as the amino group is successively methylated. Comparison of the present results with earlier data on the related amphetamines indicates that the -hydroxy group of the ephedrines decreases pH-sensitivity. The presence of this hydroxy group also enhances the metabolic stability of the drugs when compared to their amphetamine analogs under comparable urine conditions, i.e., acidic urine when renal reabsorption is negligible. Within the ephedrine series, successive N-methylation increases the metabolism of the compound; i.e., ()-norephedrine is eliminated predominantly as unchanged drug, ()-ephedrine undergoes a small amount of N-demethylation but is also excreted mainly unchanged, while ()-methylephedrine is extensively metabolized, in part to ephedrine and then to norephedrine.