Evidence map›Paper›PMID 33452585›Full record

ArticleEuropean journal of clinical pharmacology2021

Population pharmacokinetic modelling to quantify the magnitude of drug-drug interactions between amlodipine and antiretroviral drugs.

Perrine Courlet, Monia Guidi, Susana Alves Saldanha, Matthias Cavassini, Marcel Stoeckle, Thierry Buclin, Catia Marzolini, Laurent A Decosterd, Chantal Csajka

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

8 citing papers in PubMed, 10 citations in OpenAlex.

  1. Trial
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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

9 authors at 3 institutions in 1 country.

Perrine CourletService of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID https://orcid.org/0000-0001-9114-7793
Monia GuidiService of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID https://orcid.org/0000-0002-6419-9317
Susana Alves SaldanhaService of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Matthias CavassiniService of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID https://orcid.org/0000-0003-0933-7833
Marcel StoeckleDepartments of Medicine and Clinical Research, University Hospital of Basel and University of Basel, Basel, Switzerland.
Thierry BuclinService of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID https://orcid.org/0000-0003-0639-5536
Catia MarzoliniDepartments of Medicine and Clinical Research, University Hospital of Basel and University of Basel, Basel, Switzerland.ORCID https://orcid.org/0000-0002-2312-7050
Laurent A DecosterdService of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID https://orcid.org/0000-0002-9840-1325
Chantal CsajkaCentre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. chantal.csajka@chuv.ch.ORCID https://orcid.org/0000-0002-0660-082X
University of Lausanne · CHUniversity of Basel · CHUniversity of Geneva · CH

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CH) 165956Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CH) 166204
6 · The paper itself

Abstract

purposeDrug-drug interactions (DDIs) with antiretroviral drugs (ARVs) represent an important issue in elderly people living with HIV (PLWH). Amlodipine is a commonly prescribed antihypertensive drug metabolized by CYP3A4, thus predisposed to a risk of DDIs. Guidance on the management of DDIs is mostly based on theoretical considerations derived from coadministration with other CYP3A4 inhibitors. This study aimed at characterizing the magnitude of DDIs between amlodipine and ARV drugs in order to establish dosing recommendations.

methodsA population pharmacokinetic analysis was developed using non-linear mixed effect modelling (NONMEM) and included 163 amlodipine concentrations from 55 PLWH. Various structural and error models were compared to characterize optimally the concentration-time profile of amlodipine. Demographic and clinical characteristics as well as comedications were tested as potential influential covariates. Model-based simulations were performed to compare amlodipine exposure (i.e. area under the curve, AUC) between coadministered ARV drugs.

resultsAmlodipine concentration-time profile was best described using a one-compartment model with first-order absorption and a lag-time. Amlodipine apparent clearance was influenced by both CYP3A4 inhibitors and efavirenz (CYP3A4 inducer). Model-based simulations revealed that amlodipine AUC increased by 96% when coadministered with CYP3A4 inhibitors, while efavirenz decreased drug exposure by 59%.

conclusionCoadministered ARV drugs significantly impact amlodipine disposition in PLWH. Clinicians should adjust amlodipine dosage accordingly, by halving the dosage in PLWH receiving ARV with inhibitory properties (mainly ritonavir-boosted darunavir), whereas they should double amlodipine doses when coadministering it with efavirenz, under appropriate monitoring of clinical response and tolerance.

Indexed as

Models, BiologicalAgedAmlodipineAntihypertensive AgentsAnti-Retroviral AgentsArea Under CurveCytochrome P-450 CYP3ACytochrome P-450 CYP3A InducersCytochrome P-450 CYP3A InhibitorsDrug InteractionsFemaleHumansMaleMiddle AgedSocioeconomic FactorsAmlodipineAntihypertensive AgentsAnti-Retroviral AgentsCytochrome P-450 CYP3ACytochrome P-450 CYP3A InducersCytochrome P-450 CYP3A InhibitorsAmlodipineDrug-drug interactionsHIVNONMEMPharmacokinetics

Identifiers

PMID33452585
PMCPMC8184532
OpenAlexW3123418636

What OpenQuestion holds

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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.