Evidence map›Paper›PMID 20931330›Full record

ArticleEuropean journal of clinical pharmacology2011

Do CYP3A and ABCB1 genotypes influence the plasma concentration and clinical outcome of donepezil treatment?

Laura Magliulo, Marja-Liisa Dahl, Grazia Lombardi, Silvia Fallarini, Laura Maria Villa, Aldo Biolcati, Maria Gabriella Scordo

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In one paragraph

Article in European journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 3 pooled it
2.4field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 3 syntheses or guidelines pooled it, 45 citations in OpenAlex.

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  14. Influence ofPharmacogenomics and personalized medicine · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Laura MagliuloDISCAFF Department, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
Marja-Liisa Dahl
Grazia Lombardi
Silvia Fallarini
Laura Maria Villa
Aldo Biolcati
Maria Gabriella Scordo
Università degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUppsala University Hospital · SEFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico · ITOspedale Maggiore · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe aim of our study was to evaluate the impact of CYP3A4, CYP3A5, and ABCB1 polymorphisms on donepezil disposition and clinical outcome.

methodsFifty-four Italian patients diagnosed with probable mild to moderate Alzheimer's disease, treated with donepezil (37 patients 5 mg/day, 17 patients 10 mg/day) were genotyped for CYP3A4 (*1B, *3, and *4), CYP3A5 (*2, *3, and *6) and ABCB1 (3435C>T, 2677G>T/A, and 1236C>T) polymorphisms. All patients were evaluated for the degree of cognitive impairment with Mini Mental State Examination (MMSE) screening test at baseline (before treatment) and after at least 3 months of donepezil treatment at stable dose, when the drug plasma levels were measured.

resultsThree patients carried one detrimental CYP3A4 allelic variant, and 12 carried one functional CYP3A5*1 allele. No statistically significant association was found between CYP3A4 or CYP3A5 genotypes and plasma donepezil concentrations, or between genotypes and clinical response (as measured by change in MMSE score). Nine ABCB1 haplotypes were observed, the most common being 1236C/2677G/3435C (46%) and 1236T/2677T/3435T (41%). Patients homozygous for the T/T/T haplotype had slightly though not significantly lower plasma donepezil concentration-to-dose ratios than those carrying other genotypes [median (95% CI) 0.18 (0.13-0.45) vs. 0.31 (0.30-0.44) mg/l/mg/kg, respectively]. These patients also showed a slightly better clinical response (as measured by change in MMSE score) than the other genotype groups [median (95% CI) 0 (-1.3 to 3.3) vs. -1.0 (-2.1 to 0.0), respectively].

conclusionsOur data suggest that the CYP3A4 and CYP3A5 polymorphisms are unlikely to influence donepezil metabolism and/or clinical outcome. On the other hand, the ABCB1 polymorphisms may play a role in donepezil disposition and clinical outcome.

Indexed as

AdultAgedAged, 80 and overAllelesAlzheimer DiseaseATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Cytochrome P-450 CYP3ADonepezilFemaleGenotypeHumansIndansMaleMiddle AgedNootropic AgentsABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1CYP3A4 protein, humanCYP3A5 protein, humanCytochrome P-450 CYP3ADonepezilIndansNootropic AgentsPiperidines

Identifiers

PMID20931330
OpenAlexW1964441208

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.