Oxybutynin is rapidly metabolized in rat liver microsomes. Two major primary oxidation products were identified as N-desethyl oxybutynin and oxybutynin N-oxide. Deuterium substituted substrate was used to aid the identification. N-Desethyl oxybutynin was characterized by gas chromatography electron impact mass spectrometry as its trifluoroacetamide derivative and oxybutynin N-oxide was indicated by the presence of a decomposition product, 2-oxo-3-butenyl-2 cyclohexyl-2-phenylglycolate, as elucidated from the gas chromatographic mas spectrometric analysis. The formation of this product from synthetic oxybutynin N-oxide was verified and occurs by two consecutive rearrangements upon thermolysis of the unstable N-oxide. Attempted titanous chloride reduction of oxybutynin N-oxide resulted in the formation of the hydrolytic products 2-cyclohexyl-2-phenylglycolic acid and 4-diethylamino-2-butynol.
1. The absorption and excretion of delmopinol, an inhibitor of plaque formation and gingivitis, were studied in healthy male volunteers. Each subject received a single dose of a 10-ml aqueous solution of 14C-delmopinol at 2 mg/ml as a 1-min mouth rinse (the intended route of administration; n=6) or as an oral dose (n=6). 2. After mouth rinsing, 72% of the dose was expectorated. The retained portion of the dose was rapidly absorbed and eliminated. Of the dose, 25% was recovered in the urine. Renal excretion was predominant also after oral administration with 92% of the dose excreted in the urine. The total recovery of 14C-activity after 6 days was 99% (rinsing) and 95% (oral) with the bulk, 20% (rinsing) and 80% (oral), of the dose excreted already within 8 h. 3. Peak plasma levels of 14C-labelled compounds were attained at 1.5 h after rinsing and 0.5 h after oral administration; total concentrations were approximately 200 and 3000nmol/l, respectively. For parent delmopinol, peak plasma levels of 49 nmol/l (rinsing) and 8 nmol/l (oral) occurred after 1.5 and 1.3 h, respectively. After rinsing, the concentration of delmopinol declined with a half-life of 2.4 h. The plasma level of 14C-labelled compounds declined multiphasically. In the terminal elimination phase (after 72 h) remaining radioactivity, < 2% of dose (rinse) and < 5% of dose (oral), decreased with a half-life of approximately 130 and 160 h, respectively. 4. Results indicate a very low bioavailability (1-3%) due to extensive first-pass metabolism of delmopinol after oral administration. A high plasma clearance (> 60 l/h) and a large volume of distribution (> 200 l) were also indicated. 5. The results of rapid and almost complete recovery in the urine support that delmopinol can safely be used in the treatment of patients with plaque or gingivitis.
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