The metabolic fate of 14C-oxaprotiline · HCl in man. III. Stereospecific disposition

✍ Scribed by Dr. W. Dieterle; J. W. Faigle; W. Küng; W. Theobald

• Publisher: John Wiley and Sons
• Year: 1984
• Tongue: English
• Weight: 426 KB
• Volume: 5
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510050408

✦ Synopsis

The disposition of the enantiomers of oxaprotiline has been investigated after single 100 mg oral doses of racemic 14C-labelled oxaprotiline.HC1 in two healthy subjects. Absorption was complete. Peak blood concentrations of total I4C were 804 and 1010ngequiv.g-' after 4-6 h in the two subjects. After 9 days 85 and 80 per cent of the dose were excreted in urine, and a total of 93 and 87 per cent were found in the excreta.

Mean peak blood concentrations of unchanged S( +)-and R( -)-oxaprotiline amounted to 25 and l0ngg-' before, and 474 and 422ngg-I after acid hydrolysis (free plus 0glucuronide). The mean blood half-lives of the S( + ) and R( -) isomers were 22 and 23 h.

Direct 0-glucuronidation is the major metabolic pathway and N-demethylation a minor one. The former is more marked with the S( +) isomer and the latter with the R( -) isomer. For oxaprotiline, the AUC-ratio of S( +) to R( -) was 2.2 before and 1.4 after hydrolysis. For desmethyl oxaprotiline the corresponding ratio was 0.8 after hydrolysis.

In urine, 0.8 and 0.5 per cent of total I4C were present as unchanged S(+)-and R( -)-oxaprotiline. After acid hydrolysis of . the 0-glucuronides, the enantiomers account for 44.7 and 37.1 per cent. The 0-glucuronides of S( +)-and R( -)-desmethyl oxaprotiline account for 4.6 and 5.7 per cent.