ArticleEuropean journal of drug metabolism and pharmacokinetics2023
Management of Drug Interactions with Inducers: Onset and Disappearance of Induction on Cytochrome P450 3A4 and Uridine Diphosphate Glucuronosyltransferase 1A1 Substrates.
Article in European journal of drug metabolism and pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 15 citations in OpenAlex.
- Population Pharmacokinetic Modeling Practice of Time-Varying Clearance: Insights from a First-in-Human Study Case.Journal of clinical pharmacology · 2026Trial
- Pharmacokinetic Drug-Drug Interactions of DA-8010 with Clarithromycin or Rifampicin: Influence of CYP2D6 Phenotype on the Extent of These Interactions.Drug design, development and therapy · 2026Trial
- Suzetrigine Is Not Expected to Have Clinically Relevant DDIs with Apixaban and Rivaroxaban Based on PBPK Modeling.Journal of clinical pharmacology · 2026Article
- Contraceptive management in people with epilepsy: A narrative review of drug interactions, special populations, and clinical guidance.Epileptic disorders : international epilepsy journal with videotape · 2026Review
- Emergence of Integrase Strand Transfer Inhibitor Resistance Following Treatment of Latent Tuberculosis Infection in a Patient With HIV.Open forum infectious diseases · 2026Article
- Pharmacokinetic Drug-Drug Interaction of Leritrelvir in Healthy Chinese Volunteers: A Single-Arm, Open-Label, Dual-Cohort Study.Clinical drug investigation · 2026Article
- Systematic Management of a Critical CYP3A4 Interaction Between Cabozantinib and Carbamazepine: A Case Report of a Clinically Relevant Pharmacokinetic Interaction.Clinical case reports · 2026Article
- Effect of Testosterone Therapy on Cytochrome P450 3A and P-Glycoprotein Activities Using Midazolam and Digoxin as Probe Substrates Among Transgender Adults.Pharmacotherapy · 2026Article
- Pharmacokinetic evaluation of doravirine and dolutegravir during paclitaxel-based chemotherapy: a case report in an HIV-positive woman with metastatic pancreatic cancer.European journal of clinical pharmacology · 2026Article
- Dietary Modulation of CYP3A4 and Its Impact on Statins and Antidiabetic Drugs: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Lost Rate Control and Tachycardia-Induced Cardiomyopathy as a Result of an Interaction Between Enzalutamide and Diltiazem.JACC. Case reports · 2025Article
- Rifampicin-induced challenges in managing endocrine hypertension and primary aldosteronism: a case report and literature review.Frontiers in pharmacology · 2025Article
- Ideal Time to Conduct a Pharmacokinetic Investigation After Delivery to Fully Capture the Effect of Pregnancy on Drug Exposure.Open forum infectious diseases · 2024Article
- Management of enzyme de-induction in a woman with HIV on methadone maintenance switched from nevirapine- to bictegravir-based antiretroviral regimen.European journal of clinical pharmacology · 2024Article
- Article
- Assessment of Pharmacokinetic Effects of Herbal Medicines on Escitalopram.Therapeutics and clinical risk management · 2024Article
- A Case of Olanzapine Resistance from Heavy Smoking and Clinical Considerations.Kansas journal of medicineArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundPeople living with HIV may present co-morbidities requiring the initiation and subsequently the discontinuation of medications with inducing properties. The time to reach maximal enzyme induction and to return to baseline enzyme levels has not been thoroughly characterized.
objectiveThe aim of this study was to evaluate the onset and disappearance of dolutegravir [uridine diphosphate glucuronosyltransferase (UGT) 1A1 and cytochrome P450 (CYP) 3A4 substrate] and raltegravir (UGT1A1 substrate) induction with strong and moderate inducers using physiologically based pharmacokinetic (PBPK) modeling.
methodsThe predictive performance of the PBPK model to simulate dolutegravir and raltegravir pharmacokinetics and to reproduce the strength of induction was verified using clinical drug-drug interaction studies (steady-state induction) and switch studies (residual induction). The model was considered verified when the predictions were within 2-fold of the observed data. One hundred virtual individuals (50% female) were generated to simulate the unstudied scenarios. The results were used to calculate the fold-change in CYP3A4 and UGT1A1 enzyme levels upon initiation and discontinuation of strong (rifampicin) or moderate (efavirenz or rifabutin) inducers.
resultsThe time for reaching maximal induction and subsequent disappearance of CYP3A4 induction was 14 days for rifampicin and efavirenz but 7 days for rifabutin. The distinct timelines for the moderate inducers relate to their different half-lives and plasma concentrations. The induction and de-induction processes were more rapid for UGT1A1.
conclusionsOur simulations support the common practice of maintaining the adjusted dosage of a drug for another 2 weeks after stopping an inducer. Furthermore, our simulations suggest that an inducer should be administered for at least 14 days before conducting interaction studies to reach maximal induction.
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