ArticleDrug metabolism and disposition: the biological fate of chemicals2011
Complex drug interactions of HIV protease inhibitors 2: in vivo induction and in vitro to in vivo correlation of induction of cytochrome P450 1A2, 2B6, and 2C9 by ritonavir or nelfinavir.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 67 citations in OpenAlex.
- Assessment of the pharmacokinetic interaction between eltrombopag and lopinavir-ritonavir in healthy adult subjects.Antimicrobial agents and chemotherapy · 2012Trial
- Physiologically-Based Pharmacokinetic Modeling of PAXLOVID™ with First-Order Absorption Kinetics.Pharmaceutical research · 2023Article
- Combined Oral Contraceptives As Victims of Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- The inhibitory and inducing effects of ritonavir on hepatic and intestinal CYP3A and other drug-handling proteins.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Quantitative Prediction of Drug Interactions Caused by Cytochrome P450 2B6 Inhibition or Induction.Clinical pharmacokinetics · 2022Article
- The Mechanism-Based Inactivation of CYP3A4 by Ritonavir: What Mechanism?International journal of molecular sciences · 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
- Pharmacokinetics of asciminib in the presence of CYP3A or P-gp inhibitors, CYP3A inducers, and acid-reducing agents.Clinical and translational science · 2022Article
- Population pharmacokinetics of ethambutol in African children: a pooled analysis.The Journal of antimicrobial chemotherapy · 2022Article
- Drug Interactions Affecting Oral Anticoagulant Use.Circulation. Arrhythmia and electrophysiology · 2022Review
- Oral Drugs Against COVID-19.Deutsches Arzteblatt international · 2022Article
- Unraveling pleiotropic effects of rifampicin by using physiologically based pharmacokinetic modeling: Assessing the induction magnitude of P-glycoprotein-cytochrome P450 3A4 dual substrates.CPT: pharmacometrics & systems pharmacology · 2021Article
- Management of Antiretroviral Therapy with Boosted Protease Inhibitors-Darunavir/Ritonavir or Darunavir/Cobicistat.Biomedicines · 2021Review
- Genetic Polymorphism Effect on Warfarin-Rifampin Interaction: A Case Report and Review of Literature.Pharmacogenomics and personalized medicine · 2021Article
- Drug-Drug Interactions Involving Intestinal and Hepatic CYP1A Enzymes.Pharmaceutics · 2020Review
- Physiologically-Based Pharmacokinetic Modeling to Predict the Clinical Efficacy of the Coadministration of Lopinavir and Ritonavir against SARS-CoV-2.Clinical pharmacology and therapeutics · 2020Article
- The pharmacokinetic properties of HIV-1 protease inhibitors: A computational perspective on herbal phytochemicals.Heliyon · 2019Article
- A Model for Predicting the Interindividual Variability of Drug-Drug Interactions.The AAPS journal · 2017Article
- Impact of Drug Treatment at Neonatal Ages on Variability of Drug Metabolism and Drug-drug Interactions in Adult Life.Current pharmacology reports · 2017Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Drug-drug interactions (DDIs) with the HIV protease inhibitors (PIs) are complex, paradoxical (e.g., ritonavir/alprazolam), and involve multiple mechanisms. As part of a larger study to better understand these DDIs and to devise a framework for in vitro to in vivo prediction of these DDIs, we determined the inductive effect of ∼2 weeks of administration of two prototypic PIs, nelfinavir (NFV), ritonavir (RTV), and rifampin (RIF; induction positive control) on the cytochrome P450 enzymes CYP1A2, CYP2B6, CYP2C9, and CYP2D6 and the inductive or inductive plus inhibitory effect of NFV, RTV, or RIF on CYP3A and P-glycoprotein in healthy human volunteers. Statistically significant induction of CYP1A2 (2.1-, 2.9-, and 2.2-fold), CYP2B6 (1.8-, 2.4-, and 4-fold), and CYP2C9 (1.3-, 1.8-, and 2.6-fold) was observed after NFV, RTV, or RIF treatment, respectively (as expected, CYP2D6 was not induced). Moreover, we accurately predicted the in vivo induction of these enzymes by quantifying their induction by the PIs in human hepatocytes and by using RIF as an in vitro to in vivo scalar. On the basis of the modest in vivo induction of CYP1A2, CYP2B6, or CYP2C9, the in vivo paradoxical DDIs with the PIs are likely explained by mechanisms other than induction of these enzymes such as induction of other metabolic enzymes, transporters, or both.
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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.