Trial reportBritish journal of clinical pharmacology1999
Ketoconazole inhibits the metabolism of tolterodine in subjects with deficient CYP2D6 activity.
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 13 papers.
What it found
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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.
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Who cites it
13 citing papers in PubMed, 48 citations in OpenAlex.
- Trial
- Food does not influence the pharmacokinetics of a new extended release formulation of tolterodine for once daily treatment of patients with overactive bladder.Clinical pharmacokinetics · 2001Trial
- Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance.British journal of clinical pharmacology · 1999Trial
- Tolterodine does not affect the human in vivo metabolism of the probe drugs caffeine, debrisoquine and omeprazole.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
- Human hepatocytes and cytochrome P450-selective inhibitors predict variability in human drug exposure more accurately than human recombinant P450s.British journal of pharmacology · 2018Article
- Differential effects of the enantiomers of tamsulosin and tolterodine on P-glycoprotein and cytochrome P450 3A4.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Safety and tolerability profiles of anticholinergic agents used for the treatment of overactive bladder.Drug safety · 2011Review
- Evaluation of drug-drug interactions with fesoterodine.European journal of clinical pharmacology · 2009Article
- Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II.Clinical pharmacokinetics · 2009Article
- Pharmacogenetic aspects of drug-induced torsade de pointes: potential tool for improving clinical drug development and prescribing.Drug safety · 2004Review
- 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
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 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo investigate the pharmacokinetics and safety of tolterodine and tolterodine metabolites after single-and multiple-dose administration in the absence and presence of ketoconazole, an inhibitor of cytochrome P450 (CYP) 3A4, in healthy volunteers with deficient CYP2D6 activity, i.e. poor metabolisers of debrisoquine.
methodsEight healthy volunteers received single oral doses (2 mg) of tolterodine l-tartrate. Following a wash-out period of about 3 months, six of the subjects participated in a multiple-dose (1 mg twice daily) phase of the study. Ketoconazole 200 mg was given once daily for 4-4.5 days during both the single and multiple dose tolterodine administration phases. Blood samples were drawn and the pharmacokinetics of tolterodine and its metabolites were determined.
resultsA decrease (P<0.01) in apparent oral clearance of tolterodine, from 10- 12 l h-1 to 4.3-4.7 l h-1, was obtained during concomitant administration of ketoconazole, yielding at least a two-fold increase in the area under the serum concentration-time curve after single as well as after multiple doses following single dose administration of tolterodine. The mean (+/-s.d.) terminal half-life increased by 50% from 9.7+/-2.7 h to 15+/-5.4 h in the presence of ketoconazole.
conclusionsCYP3A4 is the major enzyme involved in the elimination of tolterodine in individuals with deficient CYP2D6 activity (poor metabolisers), since oral clearance of tolterodine decreased by 60% during ketoconazole coadministration. This inhibition resulted in 2.1-fold increase in AUC.
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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.