Tolterodine use for symptoms of overactive bladder

OBJECTIVE: To describe the pharmacology, pharmacokinetics, clinical efficac y, and safety of tolterodine for the treatment of overactive bladder. DATA SOURCES: Published articles and abstracts were identified from a MEDLI NE search (January 1980-October 1998) using the terms tolterodine, PNU-2005 83E, urge incontinence, overactive bladder, detrusor instability, detrusor overactivity, and antimuscarinic. Pertinent articles written in English wer e considered for review. Additional articles were identified from the bibli ographies of retrieved articles. Data from the Food and Drug Administration -approved product labeling and the manufacturer were also used in the absen ce of published data. STUDY SELECTION AND DATA EXTRACTION: Clinical studies of tolterodine involv ing human subjects were evaluated. DATA SYNTHESIS: Tolterodine is a competitive muscarinic receptor antagonist with relative functional selectivity for bladder muscarinic receptors. It is metabolized in the liver by CYP2D6 to an active metabolite (DD 01), whic h is partially responsible for its pharmacologic activity. Those who are ge netically devoid of CYP2D6 will have higher concentrations of the parent co mpound and virtually undetectable concentrations of DD 01; however, the cli nical efficacy does not appear to be altered. In dosages of 2 mg twice dail y, tolterodine has shown consistent reductions in the number of micturition s per 24 hours and less consistently decreased incontinence episodes in pat ients with detrusor overactivity. The functional selectivity of tolterodine for bladder muscarinic receptors results in fewer systemic adverse effects , such as dry mouth, than occur with comparable nonselective antimuscarinic agents. CONCLUSIONS: Clinical studies have shown that the effectiveness of tolterod ine for symptoms of overactive bladder is similar to that of oxybutynin. Th e adverse effect profiles of tolterodine and oxybutynin are similar; howeve r, comparative clinical trials have shown significantly fewer patients taki ng tolterodine require dosage reductions or discontinue therapy due to anti muscarinic adverse effects such as dry mouth. Although more costly than oxy butynin, tolterodine represents a modest improvement over oxybutynin with r espect to adverse effect profile, which may allow more patients with incont inence to tolerate therapeutic doses. Further research is necessary to dete rmine whether tolterodine has clinical advantages over similar agents in pa tients with other muscarinic adverse effects, such as constipation or cogni tive impairment.