PT  - JOURNAL ARTICLE
AU  - Tomomi Oki
AU  - Ayako Toma-Okura
AU  - Shizuo Yamada
TI  - Advantages for Transdermal over Oral Oxybutynin to Treat Overactive Bladder: Muscarinic Receptor Binding, Plasma Drug Concentration, and Salivary Secretion
AID  - 10.1124/jpet.105.094508
DP  - 2006 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1137--1145
VI  - 316
IP  - 3
4099  - http://jpet.aspetjournals.org/content/316/3/1137.short
4100  - http://jpet.aspetjournals.org/content/316/3/1137.full
SO  - J Pharmacol Exp Ther2006 Mar 01; 316
AB  - To clarify pharmacological usefulness of transdermal oxybutynin in the therapy of overactive bladder, we have characterized muscarinic receptor binding in rat tissues with measurement of plasma concentrations of oxybutynin and its metabolite N-desethyl-oxybutynin (DEOB) and salivation after transdermal oxybutynin compared with oral route. At 1 and 3 h after oral administration of oxybutynin, there was a significant increase in apparent dissociation constant (Kd) for specific [N-methyl-3H]scopolamine ([3H]NMS) binding in the rat bladder, submaxillary gland, heart, and colon compared with control values. Concomitantly, submaxillary gland and heart showed a significant decrease in maximal number of binding sites (Bmax) for [3H]NMS binding, which lasted until 24 h. Transdermal application of oxybutynin caused dose-dependent increases in Kd values for specific [3H]NMS binding in rat tissues. The increment of Kd values by transdermal oxybutynin was dependent on the application time. Plasma concentrations of oxybutynin and DEOB peaked at 1 h after oral oxybutynin. In contrast, plasma concentrations of oxybutynin increased slowly, depending on the transdermal application time of this drug until 12 h. Suppression of pilocarpine-induced salivation in rats due to transdermal oxybutynin was significantly weaker and more reversible than that by oral oxybutynin, which abolished salivary secretion. The present study has shown that transdermal oxybutynin binds significantly to rat bladder muscarinic receptors without producing both long-lasting occupation of exocrine receptors and cessation of cholinergic salivation evoked by oral oxybutynin. Thus, the present study provides further pharmacological basis for advantage of transdermal over oral oxybutynin in the therapy of overactive bladder.