Evidence map›Paper›PMID 42603181›Full record

ArticleEuropean journal of clinical pharmacology2026

Investigating PXR (NR1I2) genetic polymorphisms as possible determinants of the magnitude of the clindamycin-rifampicin pharmacokinetic interaction.

Valérie Zeller, Estelle Lu, Léo Mimram, Kamilia Brinis, Younes Kerroumi, Armelle Arnoux, Marie-Anne Loriot, Céline Narjoz, Vincent Jullien

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Article in European journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Valérie ZellerCentre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France.
Estelle LuUnité de Recherche Clinique, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Léo MimramUniversité Sorbonne Paris Nord, Infection, Antimicrobien, Modélisation, Evolution, IAME, F-93000, Bobigny, France; Université Paris Cité, F-75018, Paris, France; INSERM, U 1137, F-75018, Paris, France.
Kamilia BrinisService de Biochimie, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Younes KerroumiCentre de Référence des Infections Ostéo-Articulaires Complexes, Groupe Hospitalier Diaconesses-Croix Saint-Simon, Paris, France.
Armelle ArnouxUnité de Recherche Clinique, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Marie-Anne LoriotService de Biochimie, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Céline NarjozService de Biochimie, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.
Vincent JullienUniversité Sorbonne Paris Nord, Infection, Antimicrobien, Modélisation, Evolution, IAME, F-93000, Bobigny, France; Université Paris Cité, F-75018, Paris, France; INSERM, U 1137, F-75018, Paris, France. vincent.jullien@aphp.fr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeRifampicin is known to induce clindamycin metabolism via CYP3A4/5, but the magnitude of this interaction varies greatly from one patient to another. Because this metabolic induction results from rifampicin activation of the nuclear pregnane X receptor (PXR), the genetic polymorphisms of its NR1I2 gene and that of CYP3A4/5 might predict the risk of clindamycin underdosage when combined with rifampicin. We therefore conducted a study to determine the possible influence of NR1I2 and CYP3A4/5 gene polymorphisms on baseline and rifampicin-induced clindamycin clearance.

methodsEighty-five patients were included and sequentially received clindamycin by continuous infusion alone and then combined with rifampicin. The clindamycin steady-state concentration (CSS) was measured for each patient before and during combination therapy. Clindamycin clearance during the 2 phases was calculated as the infusion rate/CSS ratio. Five single nucleotide polymorphisms (SNPs) in the NR1I2, CYP3A4*22 and CYP3A5*3 genes were investigated.

resultsClindamycin clearances alone and with combined rifampicin were 11.29 ± 5.54 and 46.14 ± 60.13 L/h, respectively. The minimal target clindamycin CSS of 3 mg/L was not achieved in 31 patients. None of the investigated SNPs had any observed impact.

conclusionNone of the investigated SNPs can be used to predict the risk of clindamycin underdosage when combined with rifampicin. Further research is warranted to advance our understanding of this issue.

Indexed as

Anti-Bacterial AgentsClindamycinPregnane X ReceptorReceptors, SteroidRifampinAdultAgedCytochrome P-450 CYP3ACytochrome P-450 CYP3A InducersDrug InteractionsFemaleHumansMaleMiddle AgedPolymorphism, Single NucleotideAnti-Bacterial AgentsClindamycinCYP3A4 protein, humanCYP3A5 protein, humanCytochrome P-450 CYP3ACytochrome P-450 CYP3A InducersNR1I2 protein, humanPregnane X ReceptorReceptors, SteroidRifampinantibioticsdrug interactionpharmacogeneticspharmacokinetics

Identifiers

PMID42603181

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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.