Evidence map›Paper›PMID 34635995›Full record

ArticleClinical pharmacokinetics2022

Predicting Drug-Drug Interactions between Rifampicin and Ritonavir-Boosted Atazanavir Using PBPK Modelling.

Maiara Camotti Montanha, Francesc Fabrega, Alice Howarth, Nicolas Cottura, Hannah Kinvig, Fazila Bunglawala, Andrew Lloyd, Paolo Denti, Catriona Waitt, Marco Siccardi

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.9field-weighted citation impact, top 22% 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

11 citing papers in PubMed, 22 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Observational
  9. Article
  10. Pharmacokinetics and Safety of Twice-daily Ritonavir-boosted Atazanavir With Rifampicin.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024
    Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Maiara Camotti MontanhaDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK.
Francesc FabregaDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK.
Alice HowarthDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK.
Nicolas CotturaDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK.
Hannah KinvigDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK.
Fazila BunglawalaDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK.
Andrew LloydDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK.
Paolo DentiDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Catriona WaittDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK.
Marco SiccardiDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, 70 Pembroke Place, Liverpool, L69 3GF, UK. siccardi@liverpool.ac.uk.
University of Liverpool · GBUniversity of Cape Town · ZA

Funding

European and Developing Countries Clinical Trials Partnership RIA2016MC-1606
6 · The paper itself

Abstract

objectivesThe aim of this study was to simulate the drug-drug interaction (DDI) between ritonavir-boosted atazanavir (ATV/r) and rifampicin (RIF) using physiologically based pharmacokinetic (PBPK) modelling, and to predict suitable dose adjustments for ATV/r for the treatment of people living with HIV (PLWH) co-infected with tuberculosis.

methodsA whole-body DDI PBPK model was designed using Simbiology 9.6.0 (MATLAB R2019a) and verified against reported clinical data for all drugs administered alone and concomitantly. The model contained the induction mechanisms of RIF and ritonavir (RTV), the inhibition effect of RTV for the enzymes involved in the DDI, and the induction and inhibition mechanisms of RIF and RTV on the uptake and efflux hepatic transporters. The model was considered verified if the observed versus predicted pharmacokinetic values were within twofold. Alternative ATV/r dosing regimens were simulated to achieve the trough concentration (C

resultsThe PBPK model was successfully verified according to the criteria. Simulation of different dose adjustments predicted that a change in regimen to twice-daily ATV/r (300/100 or 300/200 mg) may alleviate the induction effect of RIF on ATV C

conclusionsThe developed PBPK model characterized the induction-mediated DDI between RIF and ATV/r, accurately predicting the reduction of ATV plasma concentrations in line with observed clinical data. A change in the ATV/r dosing regimen from once-daily to twice-daily was predicted to mitigate the effect of the DDI on the C

Indexed as

Anti-HIV AgentsHIV InfectionsHIV Protease InhibitorsAtazanavir SulfateDrug InteractionsHumansRifampinRitonavirAnti-HIV AgentsAtazanavir SulfateHIV Protease InhibitorsRifampinRitonavir

Identifiers

PMID34635995
PMCPMC9481493
OpenAlexW3206866701

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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 OpenQuestion graph.