Evidence map›Paper›PMID 36991285›Full record

ArticleClinical pharmacokinetics2023

General Framework to Quantitatively Predict Pharmacokinetic Induction Drug-Drug Interactions Using In Vitro Data.

Sandra Grañana-Castillo, Angharad Williams, Thao Pham, Saye Khoo, Daryl Hodge, Asangaedem Akpan, Rachel Bearon, Marco Siccardi

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Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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.

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

2 citing papers in PubMed.

  1. Article
  2. 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

8 authors.

Sandra Grañana-CastilloPharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Angharad WilliamsPharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Thao PhamPharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Saye KhooPharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Daryl HodgePharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Asangaedem AkpanInstitute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospitals NHS FT, Liverpool, UK.
Rachel BearonMathematical Sciences, University of Liverpool, Liverpool, UK.
Marco SiccardiPharmacology and Therapeutics, University of Liverpool, Liverpool, UK. siccardi@liverpool.ac.uk.ORCID 0000-0002-3539-7867

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionMetabolic inducers can expose people with polypharmacy to adverse health outcomes. A limited fraction of potential drug-drug interactions (DDIs) have been or can ethically be studied in clinical trials, leaving the vast majority unexplored. In the present study, an algorithm has been developed to predict the induction DDI magnitude, integrating data related to drug-metabolising enzymes.

methodsThe area under the curve ratio (AUC

resultsTwo independent variables were deemed significant and included in the algorithm: IVMM and fraction unbound in plasma. The observed and predicted magnitudes of the DDIs were categorised accordingly: no induction, mild, moderate, and strong induction. DDIs were assumed to be well classified if the predictions were in the same category as the observations, or if the ratio between these two was < 1.5-fold. This algorithm correctly classified 70.5% of the DDIs.

conclusionThis research presents a rapid screening tool to identify the magnitude of potential DDIs utilising in vitro data which can be highly advantageous in early drug development.

Indexed as

Cytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemCarbamazepineDrug InteractionsHumansModels, BiologicalRifampinCarbamazepineCytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemRifampin

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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.