Trial reportEuropean journal of clinical pharmacology2013
Concentration effect relationship of CYP3A inhibition by ritonavir in humans.
Trial report in European journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Model-based evaluation of the interaction between ritonavir-boosted atazanavir and rifampicin in Ugandan adults with HIV.British journal of clinical pharmacology · 2025Trial
- Time Course of the Interaction Between Oral Short-Term Ritonavir Therapy with Three Factor Xa Inhibitors and the Activity of CYP2D6, CYP2C19, and CYP3A4 in Healthy Volunteers.Clinical pharmacokinetics · 2024Trial
- Quantification of the Time Course of CYP3A Inhibition, Activation, and Induction Using a Population Pharmacokinetic Model of Microdosed Midazolam Continuous Infusion.Clinical pharmacokinetics · 2022Trial
- Simultaneous phenotyping of CYP2E1 and CYP3A using oral chlorzoxazone and midazolam microdoses.British journal of clinical pharmacology · 2019Trial
- Dose-Dependent Bioavailability and CYP3A Inhibition Contribute to Non-Linear Pharmacokinetics of Voriconazole.Clinical pharmacokinetics · 2016Trial
- Pharmacokinetic drug-drug interaction between the COVID-19 3CL protease inhibitor GST-HG171 and itraconazole in healthy subjects.Antimicrobial agents and chemotherapy · 2026Article
- Influence of a Short Course of Ritonavir Used as Booster in Antiviral Therapies Against SARS-CoV-2 on the Exposure of Atorvastatin and Rosuvastatin.Cardiovascular drugs and therapy · 2025Article
- Polypharmacy or potentially inappropriate medications among older adults with COVID-19 in a secondary hospital in China and their association with mortality.Scientific reports · 2025Article
- The interplay of poorly soluble drugs in dissolution from amorphous solid dispersions.International journal of pharmaceutics: X · 2024Article
- Pharmacokinetic analysis of placental transfer of ritonavir as a component of paxlovid using microdialysis in pregnant rats.Heliyon · 2024Article
- Physiologically-Based Pharmacokinetic Modeling of PAXLOVID™ with First-Order Absorption Kinetics.Pharmaceutical research · 2023Article
- The inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Interactions of the protease inhibitor, ritonavir, with common anesthesia drugs.Paediatric anaesthesia · 2022Review
- Clinically Relevant Interactions Between Ritonavir-Boosted Nirmatrelvir and Concomitant Antiseizure Medications: Implications for the Management of COVID-19 in Patients with Epilepsy.Clinical pharmacokinetics · 2022Review
- A Mechanistic Absorption and Disposition Model of Ritonavir to Predict Exposure and Drug-Drug Interaction Potential of CYP3A4/5 and CYP2D6 Substrates.European journal of drug metabolism and pharmacokinetics · 2022Article
- Oral Drugs Against COVID-19.Deutsches Arzteblatt international · 2022Article
- Clinically Significant Drug Interactions Between Psychotropic Agents and Repurposed COVID-19 Therapies.CNS drugs · 2021Review
- Pharmacokinetics and Toxicities of Oral Docetaxel Formulations Co-Administered with Ritonavir in Phase I Trials.Clinical pharmacology : advances and applications · 2021Article
- Composite midazolam and 1'-OH midazolam population pharmacokinetic model for constitutive, inhibited and induced CYP3A activity.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Effect of Systemic Inflammatory Response to SARS-CoV-2 on Lopinavir and Hydroxychloroquine Plasma Concentrations.Antimicrobial agents and chemotherapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the dose and concentration dependency of CYP3A inhibition by ritonavir using the established limited sampling strategy with midazolam for CYP3A activity.
methodsAn open, fixed-sequence study was carried out in 12 healthy subjects. Single ascending doses of ritonavir (0.1-300 mg) were evaluated for CYP3A inhibition in two cohorts using midazolam as a marker substance.
resultsRitonavir administered as a single oral dose produced a dose-dependent CYP3A inhibition with an ID50 of 3.4 mg. Using the measured ritonavir concentrations an exposure-inhibition effect curve was established with an IC50 of 600 h pmol/L (AUC2-4). Over the ritonavir dose range studied non-linear exposure of ritonavir was observed.
conclusionsRitonavir shows a dose and concentration effect relationship of CYP3A inhibition. In addition, a proposed auto-inhibition of ritonavir metabolism resulted in a non-linear exposure of ritonavir with sub-proportional concentrations at low doses. A time-dependent CYP3A activity may result when inhibitors of CYP3A with short elimination half-lives are used.
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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 OpenQuestion graph.