Trial reportBritish journal of clinical pharmacology2009
Inhibition of oral midazolam clearance by boosting doses of ritonavir, and by 4,4-dimethyl-benziso-(2H)-selenazine (ALT-2074), an experimental catalytic mimic of glutathione oxidase.
Trial report in British journal of clinical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 62 citations in OpenAlex.
- Early clinical pharmacology evaluation of the novel anti-inflammatory macrolide, glasmacinal (EP395): tolerability, pharmacokinetics and drug interactions.British journal of clinical pharmacology · 2026Trial
- Trial
- Pharmacokinetic Interactions between Simeprevir and Ledipasvir in Treatment-Naive Hepatitis C Virus Genotype 1-Infected Patients without Cirrhosis Treated with a Simeprevir-Sofosbuvir-Ledipasvir Regimen.Antimicrobial agents and chemotherapy · 2017Trial
- Dose-Dependent Bioavailability and CYP3A Inhibition Contribute to Non-Linear Pharmacokinetics of Voriconazole.Clinical pharmacokinetics · 2016Trial
- Concentration effect relationship of CYP3A inhibition by ritonavir in humans.European journal of clinical pharmacology · 2013Trial
- Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers.British journal of clinical pharmacology · 2013Trial
- Complex drug interactions of HIV protease inhibitors 1: inactivation, induction, and inhibition of cytochrome P450 3A by ritonavir or nelfinavir.Drug metabolism and disposition: the biological fate of chemicals · 2011Trial
- The Effects of Ritonavir on the Pharmacokinetics of Tofacitinib in Rats.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Indole-selenide derivatives: recent advances in design, synthesis and future prospects for therapeutic applications.Future medicinal chemistry · 2025Review
- Optimization of In Vitro CYP3A4 TDI Assay Conditions and Use of Derived Parameters for Clinical DDI Risk Assessment Using Static and Dynamic Models.The AAPS journal · 2025Article
- Development of a physiologically-based pharmacokinetic model for Ritonavir characterizing exposure and drug interaction potential at both acute and steady-state conditions.CPT: pharmacometrics & systems pharmacology · 2025Article
- Prediction of Pharmacokinetics for CYP3A4-Metabolized Drugs in Pediatrics and Geriatrics Using Dynamic Age-Dependent Physiologically Based Pharmacokinetic Models.Pharmaceutics · 2025Article
- Pharmacokinetic and Pharmacodynamic Interaction of Finerenone with Diltiazem, Fluconazole, and Ritonavir in Rats.European journal of drug metabolism and pharmacokinetics · 2024Article
- Physiologically-based pharmacokinetic modeling predicts the drug interaction potential of GLS4 in co-administered with ritonavir.CPT: pharmacometrics & systems pharmacology · 2024Article
- No dose adjustment of metformin or substrates of organic cation transporters (OCT)1 and OCT2 and multidrug and toxin extrusion protein (MATE)1/2K with fostemsavir coadministration based on modeling approaches.Pharmacology research & perspectives · 2024Article
- Physiologically-Based Pharmacokinetic Modeling of PAXLOVID™ with First-Order Absorption Kinetics.Pharmaceutical research · 2023Article
- 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 literature review of liver function test elevations in rifampin drug-drug interaction studies.Clinical and translational science · 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
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
what is already known about this subject* The viral protease inhibitor ritonavir is known to inhibit clearance of intravenous midazolam. * ALT-2074, a catalytic mimic of glutathione oxidase, inhibits human cytochrome P450 3A (CYP3A) isoforms in vitro. WHAT THIS STUDY ADDS: * Short-term administration of low-dose ritonavir increases area under the plasma concentration curve following oral midazolam by a factor of 28. * Therefore ritonavir is an appropriate positive control inhibitor for clinical drug interaction studies involving CYP3A substrates. * Midazolam clearance is weakly inhibited by ALT-2074, consistent with its in vitro profile.
aimsWe evaluated whether 'boosting' doses of ritonavir can serve as a positive control inhibitor for pharmacokinetic drug-drug interaction studies involving cytochrome P450 3A (CYP3A). The study also determined whether 4,4-dimethyl-benziso-(2H)-selenazine (ALT-2074), an investigational organoselenium compound that acts as a catalytic mimic of glutathione oxidase, inhibits CYP3A metabolism in vivo.
methodsThirteen healthy volunteers received single 3-mg oral doses of midazolam on three occasions: in the control condition, during co-treatment with low-dose ritonavir (three oral doses of 100 mg over 24 h), and during co-treatment with ALT-2074 (three oral doses of 80 mg over 24 h).
resultsRitonavir increased mean (+/-SE) total area under the curve (AUC) for midazolam by a factor of 28.4 +/- 4.2 (P < 0.001), and reduced oral clearance to 4.2 +/- 0.5% of control (P < 0.001). In contrast, ALT-2074 increased midazolam AUC by 1.25 +/- 0.11 (P < 0.05), and reduced oral clearance to 88 +/- 8% of control.
conclusionsLow-dose ritonavir produces extensive CYP3A inhibition exceeding that of ketoconazole (typically 10- to 15-fold midazolam AUC enhancement), and is a suitable positive control index inhibitor for drug-drug interaction studies. ALT-2074 inhibits CYP3A metabolism to a small degree that is of uncertain clinical importance.
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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.