Evidence map›Paper›PMID 28449367›Full record

ArticleBritish journal of clinical pharmacology2017

Metoprolol-pridopidine drug-drug interaction and food effect assessments of pridopidine, a new drug for treatment of Huntington's disease.

Laura Rabinovich-Guilatt, Lilach Steiner, Hussein Hallak, Gina Pastino, Pierandrea Muglia, Ofer Spiegelstein

Open access · hybridAbstract read
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Article in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact, top 95% 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

4 citing papers in PubMed, 3 citations in OpenAlex.

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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

6 authors at 3 institutions in 3 countries.

Laura Rabinovich-GuilattClinical Pharmacology & Pharmacometrics, Teva Pharmaceutical Industries Ltd, Malvern PA, USA.
Lilach SteinerDrug Metabolism and Pharmacokinetics, Teva Pharmaceutical Industries Ltd, Netanya, Israel.
Hussein HallakDrug Metabolism and Pharmacokinetics, Teva Pharmaceutical Industries Ltd, Netanya, Israel.
Gina PastinoClinical Pharmacology & Pharmacometrics, Teva Pharmaceutical Industries Ltd, Malvern PA, USA.
Pierandrea MugliaNeuroscience Discovery Medicine UCB Pharma Chemin du Foriest, Belgium.
Ofer SpiegelsteinClinical Pharmacology & Pharmacometrics, Teva Pharmaceutical Industries Ltd, Netanya, Israel.
Teva Pharmaceuticals (Israel) · ILTeva Pharmaceuticals (Czechia) · CZUCB Pharma (Belgium) · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsPridopidine is an oral drug in clinical development for treatment of patients with Huntington's disease. This study examined the interactions of pridopidine with in vitro cytochrome P450 activity and characterized the effects of pridopidine on CYP2D6 activity in healthy volunteers using metoprolol as a probe substrate. The effect of food on pridopidine exposure was assessed.

methodsThe ability of pridopidine to inhibit and/or induce in vitro activity of drug metabolizing enzymes was examined in human liver microsomes and fresh hepatocytes. CYP2D6 inhibition potency and reversibility was assessed using dextromethorphan. For the clinical assessment, 22 healthy subjects were given metoprolol 100 mg alone and concomitantly with steady-state pridopidine 45 mg twice daily. Food effect on a single 90 mg dose of pridopidine was evaluated in a crossover manner. Safety assessments and pharmacokinetic sampling occurred throughout the study.

resultsPridopidine was found to be a metabolism dependent inhibitor of CYP2D6, the main enzyme catalysing its own metabolism. Flavin-containing monooxygenase heat inactivation of liver microsomes did not affect pridopidine metabolism-dependent inhibition of CYP2D6 and its inhibition of CYP2D6 was not reversible with addition of FeCN

conclusionsAs pridopidine is a metabolism-dependent inhibitor of CYP2D6, systemic levels of drugs metabolized by CYP2D6 may increase with chronic coadministration of pridopidine. Pridopidine can be administered without regard to food.

Indexed as

Food-Drug InteractionsArea Under CurveCells, CulturedCross-Over StudiesCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsDextromethorphanDrug InteractionsFemaleFerricyanidesHealthy VolunteersHepatocytesHumansHuntington DiseaseMaleMetoprololCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsDextromethorphanferric ferricyanideFerricyanidesMetoprololPiperidinespridopidineCYP2D6drug interactionspridopidineTV-45065

Identifiers

PMID28449367
PMCPMC5595947
OpenAlexW2610021577

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Registered trials

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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.