ArticleCancer chemotherapy and pharmacology2021
Dose adjustment of venetoclax when co-administered with posaconazole: clinical drug-drug interaction predictions using a PBPK approach.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Perpetrator Characteristics of Azole Antifungal Drugs on Three Oral Factor Xa Inhibitors Administered as a Microdosed Cocktail.Clinical pharmacokinetics · 2022Trial
- Prediction of Tacrolimus-Posaconazole Interactions in Renal Transplant Patients with Different CYP3A5 Genotypes, Based on Physiological Pharmacokinetic Models.Pharmaceutics · 2026Article
- Analysis of interactions between posaconazole/voriconazole and venetoclax.Antimicrobial agents and chemotherapy · 2026Article
- Evaluating the Impact of Intestinal Bile Salts on Drug Absorption Using PBPK Modeling: Case Studies With Efavirenz, Cinnarizine, and Posaconazole.CPT: pharmacometrics & systems pharmacology · 2026Article
- From Interaction to Intervention: Intentional CYP Inhibition as a Scalable Strategy to Expand Access to High-Cost Therapies.European journal of drug metabolism and pharmacokinetics · 2026Review
- Simultaneous Determination of Venetoclax and Posaconazole in Human Plasma by UPLC-MS/MS: Application to Therapeutic Drug Monitoring in Acute Myeloid Leukemia Patients.Drug design, development and therapy · 2026Article
- Triplet regimens for all: genomically agnostic approaches to improve on HMA + VEN in AML?Hematology. American Society of Hematology. Education Program · 2025Review
- Treatment outcomes and safety of reduced‑dose venetoclax plus antifungal agents to treat acute myeloid leukemia: A single hospital experience in Taiwan.Oncology letters · 2025Article
- Chinese population may require further venetoclax dose reduction beyond guidelines when combined with voriconazole: real-world evidence from China.Frontiers in pharmacology · 2025Article
- Predicting Pharmacokinetics of Active Constituents inPharmaceuticals (Basel, Switzerland) · 2024Article
- Clinical pharmacokinetics and pharmacodynamics of venetoclax, a selective B-cell lymphoma-2 inhibitor.Clinical and translational science · 2024Review
- Managing novel therapies and concomitant medications in chronic lymphocytic leukemia: key challenges.Frontiers in pharmacology · 2024Review
- Application of physiologically based pharmacokinetics modeling in the research of small-molecule targeted anti-cancer drugs.Cancer chemotherapy and pharmacology · 2023Review
- Prediction of Omeprazole Pharmacokinetics and its Inhibition on Gastric Acid Secretion in Humans Using Physiologically Based Pharmacokinetic-Pharmacodynamic Model Characterizing CYP2C19 Polymorphisms.Pharmaceutical research · 2023Article
- Venetoclax and Azacitidine in the Treatment ofJCO precision oncology · 2023Review
- Venetoclax: A New Partner in the Novel Treatment Era for Acute Myeloid Leukemia and Myelodysplastic Syndrome.Clinical hematology international · 2023Review
- In-Depth Analysis of Physiologically Based Pharmacokinetic (PBPK) Modeling Utilization in Different Application Fields Using Text Mining Tools.Pharmaceutics · 2022Review
- Article
- Development of Physiology Based Pharmacokinetic Model to Predict the Drug Interactions of Voriconazole and Venetoclax.Pharmaceutical research · 2022Article
- The Growing Role of the BH3 Mimetic Drug Venetoclax in the Therapy of Acute Myeloid Leukemia.Mediterranean journal of hematology and infectious diseases · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeVenetoclax, a targeted anticancer agent approved for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia, is a substrate of cytochrome P450 (CYP) 3A enzyme (CYP3A4). Posaconazole, commonly used to prevent invasive fungal infections in neutropenic patients with hematological malignancies, potently inhibits CYP3A4. The purpose of this evaluation was to predict venetoclax exposures following co-administration of posaconazole at doses not previously studied clinically.
methodsTwo physiologically based pharmacokinetic (PBPK) models were developed for posaconazole based on published parameters, one for an oral suspension and another for delayed released tablets. Parameter optimization, guided by sensitivity analyses, was conducted such that the models could replicate clinical exposures of posaconazole and drug-drug interactions with sensitive CYP3A substrates including venetoclax. The clinically verified posaconazole PBPK models were then utilized to predict DDI with a previously published venetoclax PBPK model at clinically relevant dosing scenarios.
resultsThe posaconazole PBPK models predicted posaconazole exposure and DDI related fold changes with acceptable prediction errors for both posaconazole formulations. The model predicted exposures of venetoclax, when co-administered with a 300 mg QD dose of delayed release tablets of posaconazole, were in concordance with observed data. Increasing the posaconazole dose to 500 mg QD increased venetoclax exposures by about 12% relative to 300 mg QD, which were still within the venetoclax safe exposure range.
conclusionsThe posaconazole PBPK models were developed and clinically verified. Predictions using the robust PBPK model confirmed the venetoclax label recommendation of 70 mg in the presence of posaconazole at doses up to 500 mg QD.
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