ArticleBasic & clinical pharmacology & toxicology2013
Pharmacokinetic interaction between prasugrel and ritonavir in healthy volunteers.
Article in Basic & clinical pharmacology & toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04445623 (Prasugrel in the Prevention of Severe SARS-CoV2 Pneumonia in Hospitalised Patients), which is not on this map. Cited by 17 papers.
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.
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.
Prasugrel in the Prevention of Severe SARS-CoV2 Pneumonia in Hospitalised Patients
Who cites it
17 citing papers in PubMed, 44 citations in OpenAlex.
- Impact of Boosted Antiretroviral Therapy on the Pharmacokinetics and Efficacy of Clopidogrel and Prasugrel Active Metabolites.Clinical pharmacokinetics · 2018Trial
- Effect of grapefruit juice on the bioactivation of prasugrel.British journal of clinical pharmacology · 2015Trial
- 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
- Molecular Insights of SARS-CoV-2 Antivirals Administration: A Balance between Safety Profiles and Impact on Cardiovascular Phenotypes.Biomedicines · 2022Review
- Napabucasin Drug-Drug Interaction Potential, Safety, Tolerability, and Pharmacokinetics Following Oral Dosing in Healthy Adult Volunteers.Clinical pharmacology in drug development · 2021Article
- Lopinavir-Ritonavir in SARS-CoV-2 Infection and Drug-Drug Interactions with Cardioactive Medications.Cardiovascular drugs and therapy · 2021Review
- Drug interactions: a review of the unseen danger of experimental COVID-19 therapies.The Journal of antimicrobial chemotherapy · 2020Review
- Thromboembolic events and Covid-19.Advances in biological regulation · 2020Review
- Pharmacokinetics and Pharmacodynamics of Approved and Investigational P2Y12 Receptor Antagonists.Clinical pharmacokinetics · 2020Review
- Dosing Recommendations for Concomitant Medications During 3D Anti-HCV Therapy.Clinical pharmacokinetics · 2016Review
- Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450-3A in drug-drug interaction studies.British journal of clinical pharmacology · 2015Review
- A pharmacist's guide to the 2012 update of the Canadian Cardiovascular Society Guidelines for the Use of Antiplatelet Therapy.Canadian pharmacists journal : CPJ = Revue des pharmaciens du Canada : RPC · 2015Article
- Managing drug interactions in HIV-infected adults with comorbid illness.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2015Review
- Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy.Therapeutics and clinical risk management · 2015Review
- Drug interactions and antiretroviral drug monitoring.Current HIV/AIDS reports · 2014Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The new anti-aggregating agent prasugrel is bioactivated by cytochromes P450 (CYP) 3A and 2B6. Ritonavir is a potent CYP3A inhibitor and was shown in vitro as a CYP2B6 inhibitor. The aim of this open-label cross-over study was to assess the effect of ritonavir on prasugrel active metabolite (prasugrel AM) pharmacokinetics in healthy volunteers. Ten healthy male volunteers received 10 mg prasugrel. After at least a week washout, they received 100 mg ritonavir, followed by 10 mg prasugrel 2 hr later. We used dried blood spot sampling method to monitor prasugrel AM pharmacokinetics (C(max) , t(1/2) , t(max) , AUC(0-6 hr) ) at 0, 0.25, 0.5, 1, 1.5, 2, 4 and 6 hr after prasugrel administration. A 'cocktail' approach was used to measure CYP2B6, 2C9, 2C19 and 3A activities. In the presence of ritonavir, prasugrel AM C(max) and AUC were decreased by 45% (mean ratio: 0.55, CI 90%: 0.40-0.7, p = 0.007) and 38% (mean ratio: 0.62, CI 90%: 0.54-0.7, p = 0.005), respectively, while t(1/2) and t(max) were not affected. Midazolam metabolic ratio (MR) dramatically decreased in presence of ritonavir (6.7 ± 2.6 versus 0.13 ± 0.07) reflecting an almost complete inhibition of CYP3A4, whereas omeprazole, flurbiprofen and bupropion MR were not affected. These data demonstrate that ritonavir is able to block prasugrel CYP3A4 bioactivation. This CYP-mediated drug-drug interaction might lead to a significant reduction of prasugrel efficacy in HIV-infected patients with acute coronary syndrome.
Indexed as
Identifiers
What OpenQuestion holds
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.