Identification of some Urinary Metabolites of Propantheline Bromide in Man

Abstract

The peak plasma concn. of total radioactivity occurred 6 h after a single oral dose of [carboxyl-14C; methyl-2H3] propantheline bromide was administered to a healthy man. At this time 10% of the dose was present in the total plasma volume. 2. A total of 71% dose of radioactivity was excreted in urine in 96 h after dosage, 59% dose being excreted in the first 24 h. About 5.3% of the orally administered propantheline bromide was excreted unchanged. 3. T.l.c. analysis and g.l.c.-mass spectrometry showed xanthanoic acid, hydroxyxanthanoic acid(s), and propantheline as urinary metabolites of the drug. 4. A glucuronide of xanthanoic acid, a hydroxylated propantheline and the (2-hydroxyethyl)diisopropylammonium ion were tentatively identified as urinary metabolites. Hydrolysis of propantheline and conjugation of the resulting xanthanoic acid appear to be the major routes of metabolism of this compound. 5. A mean elimination half-life of 9.2 h was obtained for the total radioactivity by pharmacokinetic analysis of plasma and urine levels of 14C.

Plasma levels and urinary excretion of orally administered propantheline bromide in man

“…The urinary excretion of some 3 to 4% of the orally administered propantheline bromide unchanged is comparable with the values of 1 to 10% reported in studies using the radiolabelled compound (1,2).…”

“…The initial pharmacokinetic studies have shown that the intravenously administered drug is rapidly distributed and eliminated in man with an elimination half-life of 1 to 3 hours, and that metabolism is the major elimination route (4). The urinary excretion data were comparable to the results obtained by radioisotope techniques (1,2), with some 17.3% and 1.08% of the drug excreted unchanged after i.v, and oral administration respectively.…”

“…The compound is known to be extensively metabolized following intravenous (1) and oral administration (1,2). Thus, although some 700/0 of a dose of orally administered [l4C]-propantheline bromide was excreted in urine in man, the majority of this radioactivity was present as metabolites (1,2).…”

Pharmacokinetics of propantheline bromide in normal man.

“…This compound appears to undergo appreciable metabolism in man, even after intravenous administration (Beermann, Hellstrom & Rosen, 1972). Following oral administration of "4C-labelled propantheline bromide to normal men some 70% of the administered radioactivity was excreted in urine, but the majority of this was present as metabolites of the drug (Beermann et al, 1972;Vose, Prout, Haskins, Ford, Palmer & Tidd, 1978). These metabolites included xanthanoic acid, hydroxyxanthanoic acid, hydroxypropantheline, and a number of conjugates.…”

Propantheline bromide plasma level, urinary excretion and pharmacological data in a comparison of the bioavailability of three oral formulations of Pro-Banthine

“…PB is extensively metabolized in man, with only 17 to 20% of an i.v. dose and less than fO% of an oral dose excreted unchanged in urine (I, 3,4). The low oral absorption and extensive metabolism of PB have increased the'difficulty of its analysis in biological fluids, and pharmacological responses have been measured in studies of its availability (5,6,7).…”