ArticleCPT: pharmacometrics & systems pharmacology2021
Quantitative Assessment of Levonorgestrel Binding Partner Interplay and Drug-Drug Interactions Using Physiologically Based Pharmacokinetic Modeling.
Article in CPT: pharmacometrics & systems pharmacology, 2021. 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.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Establishing a Quantitative Framework for Combined Oral Contraceptives: Evaluating the Impact of Drug-Drug Interactions on Exposure and Clinical (Surrogate) Efficacy Endpoints.Journal of clinical pharmacology · 2025Pooled it
- Determining Critical Physiological and Drug Specific Parameters for Enhancing a Physiologically Based Pharmacokinetics Model for the Female Reproductive Tract.Pharmaceutics · 2026Article
- An open-source framework for physiologically-based pharmacokinetic modeling of kinetics in the female reproductive tract.Frontiers in pharmacology · 2026Article
- The Effect of Isoniazid for Tuberculosis Prevention on Pregnancy Risk Among Women Living With HIV on Antiretroviral Treatment and Progestin-Based Hormonal Contraception.Pharmacoepidemiology and drug safety · 2025Article
- Exploring the Feasibility of a Bracketing Approach Utilizing Modeling for Development of Long-Acting Injectables for Regulatory Approval-A Case Study Using Levonorgestrel.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Physiologically-based pharmacokinetic modeling of prominent oral contraceptive agents and applications in drug-drug interactions.CPT: pharmacometrics & systems pharmacology · 2024Article
- Combined Oral Contraceptives As Victims of Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Model-Based Analysis of In Vivo Release Data of Levonorgestrel Implants: Projecting Long-Term Systemic Exposure.Pharmaceutics · 2023Article
- Key Factors in Effective Patient-Tailored Dosing of Fluoroquinolones in Urological Infections: Interindividual Pharmacokinetic and Pharmacodynamic Variability.Antibiotics (Basel, Switzerland) · 2022Review
- Application of exposure bracketing to streamline the development of contraceptive products.Contraception: X · 2022Article
- Pharmacokinetics of the CYP3A4 and CYP2B6 Inducer Carbamazepine and Its Drug-Drug Interaction Potential: A Physiologically Based Pharmacokinetic Modeling Approach.Pharmaceutics · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Levonorgestrel (LNG) is the active moiety in many hormonal contraceptive formulations. It is typically coformulated with ethinyl estradiol (EE) to decrease intermenstrual bleeding. Due to its widespread use and CYP3A4-mediated metabolism, there is concern regarding drug-drug interactions (DDIs), particularly a suboptimal LNG exposure when co-administered with CYP3A4 inducers, potentially leading to unintended pregnancies. The goal of this analysis was to determine the impact of DDIs on the systemic exposure of LNG. To this end, we developed and verified a physiologically-based pharmacokinetic (PBPK) model for LNG in PK-Sim (version 8.0) accounting for the impact of EE and body mass index (BMI) on LNG's binding to sex-hormone binding globulin. Model parameters were optimized following intravenous and oral administration of 0.09 mg LNG. The combined LNG-EE PBPK model was verified regarding CYP3A4-mediated interaction by comparing to published clinical DDI study data with carbamazepine, rifampicin, and efavirenz (CYP3A4 inducers). Once verified, the model was applied to predict systemic LNG exposure in normal BMI and obese women (BMI ≥ 30 kg/m
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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.