Trial reportBritish journal of clinical pharmacology1999
Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance.
Trial report in British journal of clinical pharmacology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 48 citations in OpenAlex.
- Trial
- Effect of duloxetine on tolterodine pharmacokinetics in healthy volunteers.British journal of clinical pharmacology · 2004Trial
- Ketoconazole inhibits the metabolism of tolterodine in subjects with deficient CYP2D6 activity.British journal of clinical pharmacology · 1999Trial
- Tolterodine is a novel candidate for assessing CYP3A4 activity through metabolic volatiles to predict drug responses.Scientific reports · 2025Article
- Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review.Journal of clinical medicine · 2020Review
- PharmVar GeneFocus: CYP2D6.Clinical pharmacology and therapeutics · 2020Review
- Physiologically-Based Pharmacokinetic Modeling for the Prediction of CYP2D6-Mediated Gene-Drug-Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2019Article
- CYP2D6 polymorphisms and their influence on risperidone treatment.Pharmacogenomics and personalized medicine · 2016Review
- Risperidone-associated adverse drug reactions and CYP2D6 polymorphisms in a South African cohort.Applied & translational genomics · 2015Article
- Safety and tolerability profiles of anticholinergic agents used for the treatment of overactive bladder.Drug safety · 2011Review
- Quantitative prediction of cytochrome P450 (CYP) 2D6-mediated drug interactions.Clinical pharmacokinetics · 2011Article
- Using a homology model of cytochrome P450 2D6 to predict substrate site of metabolism.Journal of computer-aided molecular design · 2010Article
- Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II.Clinical pharmacokinetics · 2009Article
- Benefit-risk assessment of tolterodine in the treatment of overactive bladder in adults.Drug safety · 2004Review
- Clinical pharmacokinetics of drugs used to treat urge incontinence.Clinical pharmacokinetics · 2003Review
- Tolterodine: a review of its use in the treatment of overactive bladder.Drugs & aging · 2001Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo investigate the change in disposition of tolterodine during coadministration of the potent cytochrome P450 2D6 (CYP2D6) inhibitor fluoxetine.
methodsThirteen patients received tolterodine l-tartrate 2 mg twice daily for 2.5 days, followed by fluoxetine 20 mg once daily for 3 weeks and then concomitant administration for an additional 2.5 days. They were characterized as extensive metabolizers (EM1 with one functional CYP2D6 gene, EM2 with two functional genes) or poor metabolizers (PM).
resultsNine patients, three EM2 and four EM1 and two PM, completed the trial. Following tolterodine administration, the area under the serum concentration-time curve (AUC) of tolterodine was 4.4-times and 30-times higher among EM1 and PM, respectively, compared with EM2. The AUC of the 5-hydroxymethyl metabolite (5-HM) was not quantifiable in PM. Fluoxetine significantly decreased (P<0.002) the oral clearance of tolterodine by 93% in EM2 and by 80% in EM1. The AUC of 5-HM increased in EM2 and decreased in EM1. However, the exposure to the active moiety (unbound tolterodine +5-HM) was not significantly increased in the two phenotypes. The subdivision of the EM group showed a 2.1-fold increase in active moiety in EM2 but the exposure was still similar to EM1 compared with before the interaction.
conclusionsThe study suggests a difference in the pharmacokinetics of tolterodine and its 5-hydroxymethyl metabolite depending on the number of functional CYP2D6 genes. Fluoxetine significantly inhibited the hydroxylation of tolterodine. Despite the effect on the pharmacokinetics of tolterodine in extensive metabolizers, the clinical effect is expected to be within normal variation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.