Evidence map›Paper›PMID 35722783›Full record

ReviewClinical and translational science2022

Alternatives to rifampicin: A review and perspectives on the choice of strong CYP3A inducers for clinical drug-drug interaction studies.

Jayaprakasam Bolleddula, Sathej Gopalakrishnan, Ping Hu, Jennifer Dong, Karthik Venkatakrishnan

Open access · goldAbstract readReview
In one paragraph

Review in Clinical and translational science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Clinical Evaluation of Drug-Drug Interactions With Aficamten.Clinical and translational science · 2026
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. PBPK perspective on alternative CYP3A4 inducers for rifampin.CPT: pharmacometrics & systems pharmacology · 2022
    Article
  20. Review
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

5 authors at 2 institutions in 2 countries.

Jayaprakasam BolleddulaQuantitative Pharmacology, EMD Serono Research & Development Institute, Inc., Billerica, Massachusetts, USA.ORCID 0000-0003-4700-7819
Sathej GopalakrishnanMerck KGaA, Darmstadt, Germany.
Ping HuQuantitative Pharmacology, EMD Serono Research & Development Institute, Inc., Billerica, Massachusetts, USA.
Jennifer DongQuantitative Pharmacology, EMD Serono Research & Development Institute, Inc., Billerica, Massachusetts, USA.
Karthik VenkatakrishnanQuantitative Pharmacology, EMD Serono Research & Development Institute, Inc., Billerica, Massachusetts, USA.ORCID 0000-0003-4039-9813
Ono Pharmaceutical (United States) · USMerck (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

N-Nitrosamine (NA) impurities are considered genotoxic and have gained attention due to the recall of several marketed drug products associated with higher-than-permitted limits of these impurities. Rifampicin is an index inducer of multiple cytochrome P450s (CYPs) including CYP2B6, 2C8, 2C9, 2C19, and 3A4/5 and an inhibitor of OATP1B transporters (single dose). Hence, rifampicin is used extensively in clinical studies to assess drug-drug interactions (DDIs). Despite NA impurities being reported in rifampicin and rifapentine above the acceptable limits, these critical anti-infective drugs are available for therapeutic use considering their benefit-risk profile. Reports of NA impurities in rifampicin products have created uncertainty around using rifampicin in clinical DDI studies, especially in healthy volunteers. Hence, a systematic investigation through a literature search was performed to determine possible alternative index inducer(s) to rifampicin. The available strong CYP3A inducers were selected from the University of Washington DDI Database and their in vivo DDI potential assessed using the data from clinical DDI studies with sensitive CYP3A substrates. To propose potential alternative CYP3A inducers, factors including lack of genotoxic potential, adequate safety, feasibility of multiple dose administration to healthy volunteers, and robust in vivo evidence of induction of CYP3A were considered. Based on the qualifying criteria, carbamazepine, phenytoin, and lumacaftor were identified to be the most promising alternatives to rifampicin for conducting CYP3A induction DDI studies. Strengths and limitations of the proposed alternative CYP3A inducers, the magnitude of in vivo CYP3A induction, appropriate study designs for each alternative inducer, and future perspectives are presented in this paper.

Indexed as

Cytochrome P-450 CYP3A InducersRifampinCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsDrug InteractionsHumansCytochrome P-450 CYP3ACytochrome P-450 CYP3A InducersCytochrome P-450 CYP3A InhibitorsRifampin

Identifiers

PMID35722783
PMCPMC9468573
OpenAlexW4283158799

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.