Evidence map›Paper›PMID 38794210›Full record

ArticlePharmaceuticals (Basel, Switzerland)2024

Evaluating Drug Interactions between Ritonavir and Opioid Analgesics: Implications from Physiologically Based Pharmacokinetic Simulation.

Liang Ni, Zhihai Cao, Jiakang Jiang, Wei Zhang, Wei Hu, Qian Zhang, Chaozhuang Shen, Xijing Chen, Liang Zheng

Abstract read
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
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.

Liang NiClinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Zhihai CaoDepartment of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
Jiakang JiangDepartment of Pharmacy and Biomedical Engineering, Clinical College of Anhui Medical University, Hefei 230031, China.
Wei ZhangDepartment of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
Wei HuDepartment of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.ORCID 0000-0002-4809-7601
Qian ZhangDepartment of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.
Chaozhuang ShenDepartment of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Xijing ChenClinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Liang ZhengDepartment of Clinical Pharmacology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China.ORCID 0000-0002-4971-451X

Funding

Anhui Provincial Natural Science Foundation 2208085QH279National Natural Science Foundation of China 82204527Research Fund of Anhui Institute of Translational Medicine 2022zhyx-B10
6 · The paper itself

Abstract

Several commonly used opioid analgesics, such as fentanyl, sufentanil, alfentanil, and hydrocodone, are by report primarily metabolized by the CYP3A4 enzyme. The concurrent use of ritonavir, a potent CYP3A4 inhibitor, can lead to significant drug interactions. Using physiologically based pharmacokinetic (PBPK) modeling and simulation, this study examines the effects of different dosing regimens of ritonavir on the pharmacokinetics of these opioids. The findings reveal that co-administration of ritonavir significantly increases the exposure of fentanyl analogs, with over a 10-fold increase in the exposure of alfentanil and sufentanil when given with ritonavir. Conversely, the effect of ritonavir on fentanyl exposure is modest, likely due to additional metabolism pathways. Additionally, the study demonstrates that the steady-state exposure of hydrocodone and its active metabolite hydromorphone can be increased by up to 87% and 95%, respectively, with concurrent use of ritonavir. The extended-release formulation of hydrocodone is particularly affected. These insights from PBPK modeling provide valuable guidance for optimizing opioid dosing and minimizing the risk of toxicity when used in combination with ritonavir-containing prescriptions.

Indexed as

drug–drug interactionsfentanylhydrocodonemodeling and simulationPBPKritonavir

Identifiers

PMID38794210
PMCPMC11124264

What OpenQuestion holds

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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.