Ephedrine

Endpoint summary

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

Ephedrine plasma levels have been measured in ten asthmatic patients given a single dose of ephedrine hydrochloride (22 mg) alone before (Study A1) and after a 2 -week treatment period with ephedrine hydrochloride (11 mg) (Study A2) (Pickup 1976). In addition, same patients were given a single dose of ephedrine hydrochloride (22 mg) in combination with theophylline and a barbiturate before (Study B3) and after a 2-week treatment period with ephedrine hydrochloride (11 mg) in combination with theophylline and a barbiturate (Study B4). Pharmacokineticassessment of the data indicated no significant intra-subject changes in kinetic parameters before or after chronic treatment with ephedrine HCl (11 mg three times a day) alone or in combination. The availability of ephedrine from the tablet form, assuming each tablet contains ephedrine HCl (11 mg), was calculated as 0.88. Mean plasma half-lifes were 6.75, 6.69, 5.74, and 5.22 hours for studies Al, A2, B3, and B4, respectively. The mean clearance calculated in turn for each of the studies A1, A2, B3 and B4 was 23.3, 25.4, 28.7 and 30 litre per hour respectively. The mean volume of distribution for each of the studies was found to be 215.6, 230, 213.7 and 203.4 litres, respectively.

In the article by Feller et al. (1977) 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, D(-)-ephedrine was metabolized at a faster rate than L(+)-ephedrine, benzoic acid was formed from D(-)-ephedrine at a rate about three times greater than from the L(+)-isomer, and 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. 47-50% of the urinary 14C was attributable to hippuric acid and benzoic acid from L(+)- and D(-)-ephedrine, 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, no appreciable quantities of sulfate or glucuronide conjugates of p-hydroxylated metabolites of ephedrine or norephedrine was detectable, and small amounts (<4% of metabolites corresponding to unchanged ephedrine, norephedrine, or 1-hydroxy-l-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.