Antimuscarinic Activity of Oxybutynin in the Human Plasma Quantitated by a Radioreceptor Assay

Abstract

The antimuscarinic activity of oxybutynin was measured as oxybutynin equivalents by a radioreceptor assay (RRA). The activity was studied in plasma samples of five volunteers after a single oral dose (10 mg) or after a single intravenous dose (28 micrograms/kg) of oxybutynin hydrochloride. The results were compared to the concentrations of the drug measured by gas liquid chromatography (GLC). Following oral administration, the maximum concentration measured by RRA was significantly higher (706 nmol/l) than that by GLC (38 nmol/l). In contrast, equal concentrations were measured after intravenous administration by both methods. Metabolites with antimuscarinic activity are possibly formed through first-pass metabolism after orally administered oxybutynin. The total antimuscarinic activity of oxybutynin and its metabolites are measured by RRA, but only the parent drug by GLC.

In vivo demonstration of muscarinic receptor binding activity of N-desethyl-oxybutynin, active metabolite of oxybutynin

“…In the in vitro experiment, it has previously been shown that DEOB exerts similar anticholinergic effect as its parent compound in the human detrusor (Barras et al, 1999;Waldeck et al, 1997). Therefore, it has been suggested that DEOB is largely responsible for the anticholinergic activity after oral administration of oxybutynin (Lindeke et al, 1981;Aaltonen et al, 1984). However, the in vivo anticholinergic effects of DEOB have been little characterized.…”

Poisoning with Oxybutynin

“…Oxybutynin is rapidly absorbed following an oral dose, with peak plasma concentrations being achieved within an hour .4, 9 The absolute systemic availability is low, at around 6%, and large inter-individual variations in plasma concentration may occur.4 Practically none of the intact drug is recovered from the urine, suggesting that hepatic metabolism is the major pathway of oxybutynin inactivation.4~5 Plasma concentrations following therapeutic doses fall biexponentially, with an elimination half-life of around 2 h. In higher doses the elimination half-life is probably longer, due to a dose-related increase in the apparent volume of distribution.4 4 Possible adverse effects include a dry mouth, decreased sweating, urinary hesitancy and retention, mydriasis and failure of accommodation, tachycardia, palpitations, drowsiness, dizziness, insomnia, nausea, constipation, impotence, suppression of lactation and allergic skin reactions. Reported incidences of adverse effects vary from relatively high at 33% 6 to infrequent 7,8 at relatively similar therapeutic dose ranges.…”

Comparison of a 10-mg controlled release oxybutynin tablet with a 5-mg oxybutynin tablet in urge incontinent patients

“…Oxybutynin and its metabolite, N-desethyloxybutynin, were analyzed in serum samples by capillary gas chromatography with mass-selective detection [Aaltonen et al, 1984] (HP-5790, column HP Ultra II, Hewlett-Packard, Little Falls, DE). Diazepam was used as the internal standard.…”