ArticleCPT: pharmacometrics & systems pharmacology2023
Physiologically based pharmacokinetic modeling of tacrolimus for food-drug and CYP3A drug-drug-gene interaction predictions.
Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Impact of Intrapatient Immunosuppression Variability in Renal Transplantation Outcomes: A Systematic Review and Meta-analysis.Transplantation · 2026Pooled it
- Narrow Therapeutic Index Drugs: Regulatory Frameworks, Bioequivalence, and Model-Informed Precision Dosing.Pharmaceutics · 2026Review
- Analytical Models to Optimize Tacrolimus Dosing in Solid Organ Transplantation: A Systematic Review.Pharmaceutics · 2026Review
- In Vitro and Clinical Evaluations of UGT1A1-, P-gp-, OATP1B1-, and BCRP-Mediated Drug-Drug Interactions of Belumosudil, a Potent ROCK2 Inhibitor.Journal of clinical pharmacology · 2025Article
- A preliminary exploration of liver microsomes and PBPK to uncover the impact of CYP3A4/5 and CYP2C19 on tacrolimus and voriconazole drug-drug interactions.Scientific reports · 2025Article
- Physiologically based pharmacokinetic modeling supports investigation of potential drug-drug interactions in the pre- and early post-hematopoietic stem cell transplantation stages.Frontiers in pharmacology · 2025Article
- Analytical modelling techniques for enhancing tacrolimus dosing in solid organ transplantation: a systematic review protocol.BMJ open · 2024Article
- A physiologically-based pharmacokinetic precision dosing approach to manage dasatinib drug-drug interactions.CPT: pharmacometrics & systems pharmacology · 2024Article
- Drug-drug interactions between letermovir and tacrolimus in Japanese renal transplant recipients simulated using a physiologically based pharmacokinetic model.Frontiers in microbiology · 2024Article
- Physiologically based pharmacokinetic modeling to predict the effect of risperidone on aripiprazole pharmacokinetics in subjects with different CYP2D6 genotypes and individuals with hepatic impairment.Therapeutic advances in drug safety · 2024Article
- Association ofCurrent drug metabolism · 2024Article
- Physiologically based pharmacokinetic modeling of tacrolimus for food-drug and CYP3A drug-drug-gene interaction predictions.CPT: pharmacometrics & systems pharmacology · 2023Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunosuppressant and narrow therapeutic index drug tacrolimus is metabolized mainly via cytochrome P450 (CYP) 3A4 and CYP3A5. For its pharmacokinetics (PK), high inter- and intra-individual variability can be observed. Underlying causes include the effect of food intake on tacrolimus absorption as well as genetic polymorphism in the CYP3A5 gene. Furthermore, tacrolimus is highly susceptible to drug-drug interactions, acting as a victim drug when coadministered with CYP3A perpetrators. This work describes the development of a whole-body physiologically based pharmacokinetic model for tacrolimus as well as its application for investigation and prediction of (i) the impact of food intake on tacrolimus PK (food-drug interactions [FDIs]) and (ii) drug-drug(-gene) interactions (DD[G]Is) involving the CYP3A perpetrator drugs voriconazole, itraconazole, and rifampicin. The model was built in PK-Sim® Version 10 using a total of 37 whole blood concentration-time profiles of tacrolimus (training and test) compiled from 911 healthy individuals covering the administration of tacrolimus as intravenous infusions as well as immediate-release and extended-release capsules. Metabolism was incorporated via CYP3A4 and CYP3A5, with varying activities implemented for different CYP3A5 genotypes and study populations. The good predictive model performance is demonstrated for the examined food effect studies with 6/6 predicted FDI area under the curve determined between first and last concentration measurements (AUC
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