Trospium Chloride in the Treatment of Overactive Bladder: PHARMACOKINETICS

Less than 10% of the trospium dose is absorbed following oral administration; peak plasma concentrations (C_max) are achieved five to six hours after a single dose. Exposure causes a decrease in the C_max and an area-under-the-curve (AUC) concentration of up to 59% and 33%, respectively, for evening doses and morning doses. Because high-fat meals decrease the absorption of trospium by 70% to 80%, this agent should be taken one hour before meals or on an empty stomach.

Following a 20-mg oral dose of trospium, the apparent volume of distribution is 395 (± 140) liters, indicating that most of the ³H-trospium chloride, the radio-labeled form, is distributed in the plasma. At therapeutic concentrations, 50% to 85% of trospium is protein-bound.
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It is hypothesized that the major metabolic pathway that trospium follows is ester hydrolysis, followed by conjugation of benzylic acid to form azoniaspiro-nortropanol with glucuronic acid. The main method of elimination of trospium is via active tubular secretion, with a mean renal clearance four-fold higher than the average glomerular filtration rate. The plasma half-life is approximately 20 hours in healthy people.

Special Populations

A person’s age does not affect the pharmacokinetic profile of trospium, but anticholinergic side effects unrelated to drug exposure were often seen in patients 75 years of age or older. The incidence of commonly reported anticholinergic ADEs was higher among geriatric patients treated with trospium than among younger patients. Therefore, according to their tolerability, patients who are 75 years of age or older may receive a reduced dose of 20 mg once daily. Pharmacokinetic studies have not been performed in pediatric patients.
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TREATMENT OPTIONS

Therapeutic options for the management of OAB include both medication and behavioral therapy. Antimuscarinic agents with tertiary or quaternary amines remain the first-line (medicinal) therapy for the OAB. These agents reduce urge, stabilize detrusor overactivity, and increase bladder capacity.Patient education, keeping a voiding diary, managing fluid and diet, timed or prophylactic voiding, pelvic floor exercises, and delayed voiding are behavioral therapies that should be used in conjunction with medicinal therapy. Alternative treatments for OAB include bladder training, electrical stimulation, and surgery in severe cases, if all other treatments have failed.