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Clinical Pharmacokinetics of Trospium Chloride

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Abstract

Trospium chloride, a quaternary amine with anticholinergic properties, is used for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and urinary frequency. The pharmacokinetics of trospium chloride have been investigated in healthy volunteers, in patients with renal and hepatic impairment, and in those with symptoms of overactive bladder, after oral, intravenous and intravesical administration.

After oral administration, absorption of the hydrophilic trospium chloride is slow and incomplete. Peak plasma concentrations (Cmax) of approximately 4 ng/mL are reached 4–5 hours after administration of a 20mg immediate-release preparation. The mean bioavailability is approximately 10% and decreases by concomitant food intake (to a mean of 26% of the fasting area under the plasma concentration-time curve [AUC]). Trospium chloride displays dose proportional increases in AUC and Cmax after a single dose within the clinically relevant dose range (20–60mg). The mean volume of distribution is approximately 350–800L. The drug is minimally (mean approximately 10%) metabolised to spiroalcohol by hydrolysis, is 50% plasma protein bound and does not cross the blood-brain barrier. Urinary excretion of the parent compound plays a major role in the disposition of the drug, with a mean renal clearance of 29 L/h (accounting for approximately 70% of total clearance) and a mean elimination half-life ranging from 10 to 20 hours. Elimination of the drug is slowed in patients with renal insufficiency, and population pharmacokinetic modelling has demonstrated that drug clearance is correlated with serum creatinine concentration. Thus, dose reduction is needed in patients with severe renal impairment (i.e. creatinine clearance <30 mL/min).

To date, no clinically relevant pharmacokinetic drug-drug interactions have been identified; the drug does not bind to any of the drug metabolising cytochrome P450 enzymes.

The pharmacokinetics of the drug are compatible with twice-daily administration. A once-daily schedule may also be appropriate, but this regimen needs formal clinical evaluation.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

Data of several unpublished studies were supplied by MADAUS AG, Köln, Germany. Alexander Jetter and Uwe Fuhr received financial support for several pharmacokinetic studies on trospium chloride from MADAUS AG. In adherence with the guidelines of the International Committee of Medical Journal Editors, the authors declare they have no other conflict of interest directly relevant to the content of this review.

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Authors and Affiliations

  1. Department of Pharmacology, Clinical Pharmacology Unit, University of Cologne, Cologne, Germany

    Oxana Doroshyenko, Alexander Jetter &  Uwe Fuhr

  2. MADAUS AG, Köln, Germany

    Karl P. Odenthal

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  1. Oxana Doroshyenko
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  2. Alexander Jetter
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  3. Karl P. Odenthal
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  4. Uwe Fuhr
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Correspondence to Uwe Fuhr.

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Doroshyenko, O., Jetter, A., Odenthal, K.P. et al. Clinical Pharmacokinetics of Trospium Chloride. Clin Pharmacokinet 44, 701–720 (2005). https://doi.org/10.2165/00003088-200544070-00003

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