Advantages for Transdermal over Oral Oxybutynin to Treat Overactive Bladder: Muscarinic Receptor Binding, Plasma Drug Concentration, and Salivary Secretion

Abstract

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 Ndesethyl-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 (K d ) for specific [N-methyl- 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.

Transdermal delivery of oxybutynin chloride proniosomal gels for the treatment of overactive bladder

“…Chemical irritation caused by ACA produces acute inflammation of the urinary bladder and, consequently, facilitates micturition in rats (Oki et al, 2006).…”

“…Rats were anaesthetized with diethyl ether. Effects of proniosomal gels and oral administration of OC given 1, 3, 12 and 24 h after pilocarpine (cumulative dose)-induced salivary secretion were examined (Oki et al, 2006).…”

“…Measurement of salivary secretion was undertaken according to the method described by Oki et al (2006). Rats were anaesthetized with diethyl ether.…”

Transdermal delivery of tolterodine tartrate for overactive bladder treatment: In vitro and in vivo evaluation

“…A urinary catheter was used to administer the solution to unconscious rats. This model produces micturition due to the acute infl ammation caused in the urinary bladder by ACA (21).…”

“…The experiment was conducted on diethyl ether anesthetized rats (21). Cott on balls (3-5) were kept for 10 mins for saliva absorption; they were immediately weighed to avoid moisture loss.…”