Evidence map›Paper›PMID 25465228›Full record

ArticleEuropean journal of drug metabolism and pharmacokinetics2016

Safety and pharmacokinetics of the CIME combination of drugs and their metabolites after a single oral dosing in healthy volunteers.

Natacha Lenuzza, Xavier Duval, Grégory Nicolas, Etienne Thévenot, Sylvie Job, Orianne Videau, Céline Narjoz, Marie-Anne Loriot, Philippe Beaune, Laurent Becquemont and 6 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in European journal of drug metabolism and pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01188525 (Pharmacokinetic of Ten Parent Drugs and Their Metabolits in Order to Characterise Individual Metabolic Profile), which is not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

NCT01188525 phase1completednot on this map

Pharmacokinetic of Ten Parent Drugs and Their Metabolits in Order to Characterise Individual Metabolic Profile

TypeinterventionalSponsorInstitut National de la Santé Et de la Recherche Médicale, FranceRan2010 to 2011Enrolled10ConditionsHealthy VolunteersArms10 parents drugs adminstration
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  3. Review
  4. Article
  5. Article
  6. Article
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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

16 authors.

Natacha LenuzzaCEA, LIST, Data Analysis and Systems Intelligence Laboratory, Gif-sur-Yvette, France.
Xavier DuvalClinical Investigation Center (CIC-1425), CHU Bichat Claude Bernard, Paris, France.
Grégory NicolasCEA, DSV, iBiTecS, Pharmacology and Immunoanalysis Unit, Gif-sur-Yvette, France.
Etienne ThévenotCEA, LIST, Data Analysis and Systems Intelligence Laboratory, Gif-sur-Yvette, France.
Sylvie JobCEA, LIST, Data Analysis and Systems Intelligence Laboratory, Gif-sur-Yvette, France.
Orianne VideauCEA, DSV, iBiTecS, Pharmacology and Immunoanalysis Unit, Gif-sur-Yvette, France.
Céline NarjozDepartment of Biochemistry, Pharmacogenetics and Molecular Oncology Unit, Assistance Publique des Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
Marie-Anne LoriotDepartment of Biochemistry, Pharmacogenetics and Molecular Oncology Unit, Assistance Publique des Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
Philippe BeauneDepartment of Biochemistry, Pharmacogenetics and Molecular Oncology Unit, Assistance Publique des Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
Laurent BecquemontClinical Research Unit EA2706 Paris sud-CHU Bicêtre, Le Kremlin Bicêtre, France.
France MentréINSERM, IAME, UMR1137, University Paris-Diderot, Sorbonne Paris Cité, Paris, France.
Christian Funck-BrentanoDepartment of Pharmacology and UMR ICAN 1166, Faculty of Medicine, Sorbonne University, UPMC Univ Paris 06, Paris, France.
Loubna AlavoineClinical Investigation Center (CIC-1425), CHU Bichat Claude Bernard, Paris, France.
Philippe ArnaudPharmacy, CHU Bichat Claude Bernard, Paris, France.
Marcel DelaforgeCEA, DSV, iBiTecS, UMR 8221, Bioenergetics, Structural Biology and Mechanisms Unit, Gif-sur-Yvette, France.
Henri BénechCEA, DSV, iBiTecS, Pharmacology and Immunoanalysis Unit, Gif-sur-Yvette, France. henri.benech@cea.fr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This phase I, pilot clinical study was designed to evaluate the safety and the pharmacokinetic (PK) profiles of the CIME (Metabolic Identity Card) combination of ten drugs, with a view to its use as a phenotyping cocktail. Ten healthy Caucasian subjects were orally dosed with the CIME combination (caffeine-CYP1A2, repaglinide-CYP2C8, tolbutamide-CYP2C9, omeprazole-CYP2C19, dextromethorphan-CYP2D6, midazolam-CYP3A, acetaminophen-UGT1A1, 6&9 and 2B15, digoxin-P-gp, rosuvastatin-OATP1B1&3 and memantine-active renal transport). Blood was collected over 3 days and on day 7. CIME probes and relevant metabolites were assayed by LC-MS/MS and PK parameters were calculated. Main results were: (1) good safety with reversible mild or moderate adverse effects, (2) an analytical method able to quantify simultaneously the 10 probes and the major metabolites, (3) calculation of PK parameters for all probes in general agreed with published values, and (4) identification of the low CYP2D6 metabolizer. This pilot study showed that the CIME combination was well tolerated and that its pharmacokinetics could be accurately measured in healthy volunteers. This combination can now confidently be checked for sensitivity and specificity and for lack of interaction to be validated as a phenotyping cocktail.

Indexed as

Drug InteractionsAdministration, OralAdultCytochrome P-450 Enzyme SystemDrug-Related Side Effects and Adverse ReactionsFemaleHealthy VolunteersHumansMalePharmaceutical PreparationsPilot ProjectsYoung AdultCytochrome P-450 Enzyme SystemPharmaceutical PreparationsCIMEPharmacokineticsPhase IProbesSafety

Identifiers

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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.