ArticleCPT: pharmacometrics & systems pharmacology2022
Robust physiologically based pharmacokinetic model of rifampicin for predicting drug-drug interactions via P-glycoprotein induction and inhibition in the intestine, liver, and kidney.
Article in CPT: pharmacometrics & systems pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Quantitative prediction of intravenous drug interactions caused by cytochromes P450 inhibitors and inducers.British journal of clinical pharmacology · 2026Article
- Exposure to azithromycin and the effect of co-administration of rifampicin in patients with non-tuberculous mycobacterial disease.The Journal of antimicrobial chemotherapy · 2026Article
- Assessing transporter-mediated rifampin-linezolid interaction using physiologically-based pharmacokinetic modelling.British journal of clinical pharmacology · 2026Article
- Biodistribution of Cerivastatin, Repaglinide, Glyburide, Rosuvastatin, and Valsartan in Cynomolgus Monkeys and PBPK Analysis.The AAPS journal · 2026Article
- Characterizing Apixaban Pharmacokinetics Through Physiologically-Based Pharmacokinetic Modeling: Critical Role of Biliary Secretion and Enterohepatic Circulation in Humans.CPT: pharmacometrics & systems pharmacology · 2026Article
- Elucidating Contributions of Drug Transporters/Enzyme to Nonlinear Pharmacokinetics of Grazoprevir by PBPK Modeling With a Cluster Gauss-Newton Method.CPT: pharmacometrics & systems pharmacology · 2025Article
- Building Confidence in Physiologically Based Pharmacokinetic Modeling of CYP3A Induction Mediated by Rifampin: An Industry Perspective.Clinical pharmacology and therapeutics · 2025Review
- Pre-ADMET studies of 5-(3',4'-dihydroxyphenyl)-γ-valerolactone, the bioactive intestinal metabolite of proanthocyanidins.Archiv der Pharmazie · 2025Article
- The Development of an Age-Appropriate Fixed Dose Combination for Tuberculosis Using Physiologically-Based Pharmacokinetic Modeling (PBBM) and Risk Assessment.Pharmaceutics · 2024Article
- Physiologically-based pharmacokinetic modeling for investigating the effect of simeprevir on concomitant drugs and an endogenous biomarker of OATP1B.CPT: pharmacometrics & systems pharmacology · 2023Article
- Physiologically-based pharmacokinetic modeling of quinidine to establish a CYP3A4, P-gp, and CYP2D6 drug-drug-gene interaction network.CPT: pharmacometrics & systems pharmacology · 2023Article
- Physiologically-based pharmacokinetic pharmacodynamic parent-metabolite model of edoxaban to predict drug-drug-disease interactions: M4 contribution.CPT: pharmacometrics & systems pharmacology · 2023Article
- Research Methods and New Advances in Drug-Drug Interactions Mediated by Renal Transporters.Molecules (Basel, Switzerland) · 2023Review
- Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats.Pharmaceutics · 2023Article
- The Issue of Pharmacokinetic-Driven Drug-Drug Interactions of Antibiotics: A Narrative Review.Antibiotics (Basel, Switzerland) · 2022Review
- Robust physiologically based pharmacokinetic model of rifampicin for predicting drug-drug interactions via P-glycoprotein induction and inhibition in the intestine, liver, and kidney.CPT: pharmacometrics & systems pharmacology · 2022Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P-glycoprotein (P-gp) is an efflux transporter that plays an important role in the pharmacokinetics of its substrate, and P-gp activities can be altered by induction and inhibition effects of rifampicin. This study aimed to establish a physiologically based pharmacokinetic (PBPK) model of rifampicin to predict the P-gp-mediated drug-drug interactions (DDIs) and assess the DDI impact in the intestine, liver, and kidney. The induction and inhibition parameters of rifampicin for P-gp were estimated using two of seven DDI cases of rifampicin and digoxin and incorporated into our previously constructed PBPK model of rifampicin. The constructed rifampicin model was verified using the remaining five DDI cases with digoxin and five DDI cases with other P-gp substrates (talinolol and quinidine). Based on the established PBPK model, following repeated dosing of 600 mg rifampicin, the deduced net effect was an approximately threefold induction in P-gp activities in the intestine, liver, and kidney. Furthermore, in all 12 cases the predicted area under the plasma concentration-time curve ratios of the P-gp substrates were within the predefined acceptance criteria with various dosing regimens. Intestinal effects of P-gp-mediated DDIs had their greatest impact on the pharmacokinetics of digoxin and talinolol, with a minimal impact on the liver and kidney. For quinidine, predicted intestinal P-gp/cytochrome P450 3A-mediated DDIs were slightly underestimated because of the complexity of nonlinearity and transporter-enzyme interplay. These findings demonstrate that our rifampicin model can be applicable to quantitatively predict the net impact of P-gp induction and/or inhibition on diverse P-gp substrates and investigate the magnitude of DDIs in each tissue.
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