METABOLISM OF ORPHENADRINE CITRATE IN MAN

¹ Riker Laboratories, Northridge, California; Cedars-Sinai Medical Center; University of California, California College of Medicine, Irvine, California; Veterans Administration Hospital, Sepulveda, California
² Riker Laboratories, Northridge, California; Cedars-Sinai Medical Center; University of California, California College of Medicine, Irvine, California; the Veterans Administration Hospital, Sepulveda, California

The absorption, excretion and metabolism of tritium-labeled N,N-dimethyl-2(o-methyl--phenylbenzyloxy) ethylamine citrate (orphenadrine citrate) were Studied in four healthy male volunteers after iv. and p.o. administration (capsule and matrix tablet). The drug was equally well absorbed from either solid dosage form. Blood levels of orphenadrine regardless of the route of administration are very low as a result of rapid distribution into tissue depots characteristic of most basic compounds. Urinary excretion studies showed no statistical differences in the amount of radioactivity excreted in 72 hours (60%). Orphenadrine undergoes rapid and extensive biotransformation with only 8% of the administered dose excreted unchanged. Eight metabolites were quantified and identified in the urine by thin-layer chromatography. The chromatograms were developed with absolute ethanol and NH, (28-30%) (50:1 v/v). The major urinary metabolites were identified as follows (percentage of the administered dose): orphenadrine (82%), N-monodemethylorphenadrine (8.1%), N,N-didemethylorphendrine (4.4%), orphenadrine N-oxide (4.6%), glucuronide/sulfate of o-methylbenzhydrylosxyacetic acid (13.0%) and o-methylbenzhydrol (82%). The minor metabolites were o-methylbenzhydrol (0.4%) and o-methylbenzhydryloxyacetic acid (0.2%).