ReviewBritish journal of clinical pharmacology2015
Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450-3A in drug-drug interaction studies.
Review in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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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.
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.
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Who cites it
38 citing papers in PubMed, 103 citations in OpenAlex.
- Osimertinib Cost Minimization in Non-Small Cell Lung Cancer (NSCLC) Treatment: Hypothesis Generation for a Population Pharmacokinetic Approach for Equivalent Dose Optimization of Osimertinib in Combination with Cobicistat.Journal of clinical pharmacology · 2025Trial
- Effect of Cytochrome P450 3A Inhibition and Induction by Itraconazole and Rifampin on Tazemetostat Pharmacokinetics in Patients With Advanced Malignancies.Clinical pharmacology in drug development · 2025Trial
- Single- and multiple-dose pharmacokinetics and safety of the SARS-CoV-2 3CL protease inhibitor RAY1216: a phase 1 study in healthy participants.Antimicrobial agents and chemotherapy · 2025Trial
- Effect of 3 Single Doses of Trazodone on QTc Interval in Healthy Subjects.Journal of clinical pharmacology · 2020Trial
- A First-in-Human Trial of GLS4, a Novel Inhibitor of Hepatitis B Virus Capsid Assembly, following Single- and Multiple-Ascending-Oral-Dose Studies with or without Ritonavir in Healthy Adult Volunteers.Antimicrobial agents and chemotherapy · 2019Trial
- Amenamevir: Studies of Potential CYP3A-Mediated Pharmacokinetic Interactions With Midazolam, Cyclosporine, and Ritonavir in Healthy Volunteers.Clinical pharmacology in drug development · 2018Trial
- Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when coadministered with dual or selective CYP2C9 and CYP3A interacting drugs.British journal of clinical pharmacology · 2018Trial
- Pharmacokinetic interaction between the CYP3A4 inhibitor ketoconazole and the hormone drospirenone in combination with ethinylestradiol or estradiol.British journal of clinical pharmacology · 2015Trial
- Assessing the Influence of CYP3A4 Inhibitors on Voriconazole Exposure across CYP2C19 Genotypes: A Physiologically Based Pharmacokinetic Model Analysis.Clinical pharmacokinetics · 2026Article
- The Effects of Ritonavir on the Pharmacokinetics of Tofacitinib in Rats.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Evaluation of Potential Effects of CYP3A Inhibition and CYP3A Induction on the Pharmacokinetics of Fruquintinib in Healthy Subjects.Clinical pharmacology in drug development · 2025Article
- Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions of Soticlestat as a Victim of CYP Induction and Inhibition, and as a Perpetrator of CYP and P-Glycoprotein Inhibition.Clinical pharmacology in drug development · 2025Article
- Ritonavir's Evolving Role: A Journey from Antiretroviral Therapy to Broader Medical Applications.Current oncology (Toronto, Ont.) · 2024Review
- Pharmacokinetic analysis of placental transfer of ritonavir as a component of paxlovid using microdialysis in pregnant rats.Heliyon · 2024Article
- Simultaneous Prediction Method for Intestinal Absorption and Metabolism Using the Mini-Ussing Chamber System.Pharmaceutics · 2023Review
- Assessment of Drug-Drug Interaction Risk Between Intravenous Fentanyl and the Glecaprevir/Pibrentasvir Combination Regimen in Hepatitis C Patients Using Physiologically Based Pharmacokinetic Modeling and Simulations.Infectious diseases and therapy · 2023Article
- The inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Review
- Effects of CYP3A Inhibition, CYP3A Induction, and Gastric Acid Reduction on the Pharmacokinetics of Ripretinib, a Switch Control KIT Tyrosine Kinase Inhibitor.Clinical pharmacology in drug development · 2022Article
- The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe regulatory prohibition of ketoconazole as a CYP3A index inhibitor in drug-drug interaction (DDI) studies has compelled consideration of alternative inhibitors.
methodsThe biomedical literature was searched to identify DDI studies in which oral midazolam (MDZ) was the victim, and the inhibitory perpetrator was either ketoconazole, itraconazole, clarithromycin, or ritonavir. The ratios (RAUC ) of total area under the curve (AUC) for MDZ with inhibitor divided by MDZ AUC in the control condition were aggregated across individual studies for each inhibitor.
resultsMean (± SE) RAUC values were: ketoconazole (15 studies, 131 subjects), 11.5 (±1.2); itraconazole (five studies, 48 subjects), 7.3 (±1.0); clarithromycin (five studies, 73 subjects), 6.5 (±10.9); and ritonavir (13 studies, 159 subjects), 14.5 (±2.0). Differences among inhibitors were significant (F = 5.31, P < 0.005). RAUC values were not significantly related to inhibitor dosage or to duration of inhibitor pre-exposure prior to administration of MDZ.
conclusionsRitonavir produces CYP3A inhibition equivalent to or greater than ketoconazole, and is the best index CYP3A inhibitor alternative to ketoconazole. Cobicistat closely resembles ritonavir in structure and function, and can also be considered. Itraconazole and clarithromycin are not suitable alternatives since they do not produce inhibition comparable with ketoconazole or ritonavir, and have other significant disadvantages as well.
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Registered trials
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.