Beyond The Abstract Effect Of Tolterodine On Sleep Structure Modulated By CYP2D6 Genotype new study1 presented a novel genotyping analysis of the data in the two previous studies on the effect of tolterodine on sleep in healthy sleepers2, 3 In previous studies, we have a significant reduction of REM sleep, when the single dose of tolterodine compared to placebo2. This effect was particularly pronounced in healthy volunteers aged 50 years3 compared to young healthy volunteers.

The new study with the aim to investigate whether tolterodine impact on the structure of sleep could be further explained by another CYP2D6 metabolizer. To this end, we pooled data from the two earlier studies in a retrospective analysis, and were able to use 44 volunteers in total. Analysis for the CYP2D6 alleles 3, 4, 5, 6 and the reproduction. We found 19 extensive metabolizer with two active alleles of CYP2D6, 20 intermediate metabolizers a defective allele, 4 poor metabolizers with two alleles defective, and a ultrareapid metabolizer with a CYP6D2 gene duplication, combined with a wild type allele.
The analysis showed a significant reduction in REM sleep duration in the group with one or more defective alleles (ie, in the intermediate and poor metabolizers). Additionally, in the poor metabolizers all 4 subjects showed a reduction of REM sleep. The clinical significant reduction in REM sleep in the sub-group could explain some of the reported side effects such as drowsiness, although no significant differences between the groups in the context of this subjective sleep parameters were observed. We must admit that our subgroup analysis suffers from the small sample size and limits of the interpretation of our results somewhat. To have enough poor metabolizers a much gr�ere study would be required, and only then conclusions could be drawn if the metabolizer status can be conclusively explain the side effect of sleepiness in patients with tolterodine.

1 References Diefenbach K, K Jaeger, Wollny A, Penzel T, Fietze I, Roots I. effect of tolterodine on sleep modulated structure of CYP2D6 genotype. Sleep Medicine (2007) doi: 10.1016/j.sleep.2007.07.019 (Articles in the press).

2 Diefenbach K, F Donath, Maurer A, Quispe Bravo S, Wernecke KD, Schwantes U, Hazel Mann J, Roots I. randomized, double-blind study on the effects of oxybutynin, tolterodine, trospium chloride and placebo on sleep in healthy young volunteers. Drug Clin Invest 23: 395-404 (2003) .

3 Diefenbach K, Arold G, Wollny A, Schwantes U, Hazel Mann J, Roots I. effects on the sleep of anticholinergics for overactive bladder treatment in healthy volunteers aged > = 50 years. BJU International 95: 346-349 (2005).

Written by Constance
Diefenbach, MD, Katrin Jaeger, MD, Agnes Wollny, MD, Thomas Penzel, MD , Ingo Fietze, MD, and Ivar Roots, MD, as part of the Beyond the summary at This initiative provides a way for the publication of the professional Urology. writers are a possibility on the circumstances, restrictions, etc.. . your research by referencing the published abstract.

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