Intravesical instillation of human urine after oral administration of trospium, tolterodine and oxybutynin in a rat model of detrusor overactivity.
OBJECTIVE
To study the effects of antimuscarinics excreted into human urine on normal bladder in a rat model of detrusor overactivity.


METHODS
Two 'normal' adult volunteers collected voided urine after taking trospium (20 mg, twice daily), tolterodine LA (4 mg, four times daily), or oxybutynin XL (10 mg, four times daily). The drugs were taken in a random order for 5 days with a 7-day washout period between the drugs. The urine collected from the two volunteers was mixed together and then blindly labelled and used for testing. Control human urine (no oral antimuscarinics) was also used. The effect of intravesical administration of human urine on carbachol-induced bladder overactivity was studied in female Sprague-Dawley rats anaesthetised with urethane. Cystometric variables during continuous infusion (0.04 mL/min) for >1 h each of saline, human urine, then a mixture of carbachol (30 microm) and human urine were compared in the four groups (control and the three different antimuscarinics tested; six rats per group).


RESULTS
Human urine, with or with no intake of antimuscarinic agents, had no effect on normal bladder function. Bladder capacity and intercontraction intervals were significantly decreased after adding carbachol to urine containing vehicle, tolterodine or oxybutynin. However, urine collected from the humans who had taken trospium prevented the carbachol-induced reduction in bladder capacity and intercontraction intervals. Maximum voiding pressure and pressure threshold were not changed in any case.


CONCLUSIONS
This is the first report that the urine excreted after oral ingestion of trospium (20 mg, twice daily) has a significant inhibitory effect in a rat model of detrusor overactivity. This suggests that antimuscarinic agents have a local bladder effect during the bladder-storage phase in addition to the smooth muscle-mediated voiding phase.
Kim
Yongtae
Y
Department of Urology, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
Yoshimura
Naoki
N
Masuda
Hitoshi
H
De Miguel
Fernando
F
Chancellor
Michael B
MB
D000283:Administration, Intravesical; D000704:Analysis of Variance; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000652:urine*; D003408:Cresols / Q000494:pharmacology / Q000652:urine*; D005260:Female; D006801:Humans; D008333:Mandelic Acids / Q000494:pharmacology / Q000652:urine*; D018727:Muscarinic Antagonists / Q000494:pharmacology / Q000652:urine*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D010665:Phenylpropanolamine / Q000494:pharmacology / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068737:Tolterodine Tartrate; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D014549:Urinary Incontinence / Q000188:drug therapy*
D001559:Benzhydryl Compounds; D003408:Cresols; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C005419:oxybutynin