ArticleThe AAPS journal2016
Pharmacokinetic Interactions for Drugs with a Long Half-Life—Evidence for the Need of Model-Based Analysis.
Article in The AAPS journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review.Clinical pharmacokinetics · 2017Pooled it
- Relative bioavailability of delamanid 50 mg tablets dispersed in water in healthy adult volunteers.British journal of clinical pharmacology · 2025Trial
- Population Pharmacokinetic Analysis of Bedaquiline-Clarithromycin for Dose Selection Against Pulmonary Nontuberculous Mycobacteria Based on a Phase 1, Randomized, Pharmacokinetic Study.Journal of clinical pharmacology · 2021Trial
- Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis.Antimicrobial agents and chemotherapy · 2021Trial
- Population Pharmacokinetics of Cladribine in Patients with Multiple Sclerosis.Clinical pharmacokinetics · 2017Trial
- Population Pharmacokinetics of Bedaquiline and Metabolite M2 in Patients With Drug-Resistant Tuberculosis: The Effect of Time-Varying Weight and Albumin.CPT: pharmacometrics & systems pharmacology · 2016Trial
- Clinical assessment of mocravimod as a victim of drug-drug interactions via CYP3A4 metabolism and transporters.Clinical pharmacology in drug development · 2026Article
- Drug-Drug Interactions in Nosocomial Infections: An Updated Review for Clinicians.Pharmaceutics · 2024Review
- Managing Modern Antiretroviral Therapy in the Intensive Care Unit: Overcoming Challenges for Critically Ill People With Human Immunodeficiency Virus.Open forum infectious diseases · 2024Review
- An experience on the model-based evaluation of pharmacokinetic drug-drug interaction for a long half-life drug.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
- Physiologically-Based Pharmacokinetic Modeling to Support the Clinical Management of Drug-Drug Interactions With Bictegravir.Clinical pharmacology and therapeutics · 2021Article
- Clofazimine pharmacokinetics in patients with TB: dosing implications.The Journal of antimicrobial chemotherapy · 2020Article
- Relative bioavailability of bedaquiline tablets suspended in water: Implications for dosing in children.British journal of clinical pharmacology · 2018Article
- The Role of Therapeutic Drug Monitoring in Mycobacterial Infections.Microbiology spectrum · 2017Review
- Simulation studies on the estimation of total area under the curve in the presence of right-tailed censoring.Journal of pharmacokinetics and pharmacodynamics · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Pharmacokinetic drug-drug interactions (DDIs) can lead to undesired drug exposure, resulting in insufficient efficacy or aggravated toxicity. Accurate quantification of DDIs is therefore crucial but may be difficult when full concentration-time profiles are problematic to obtain. We have compared non-compartmental analysis (NCA) and model-based predictions of DDIs for long half-life drugs by conducting simulation studies and reviewing published trials, using antituberculosis drug bedaquiline (BDQ) as a model compound. Furthermore, different DDI study designs were evaluated. A sequential design mimicking conducted trials and a population pharmacokinetic (PK) model of BDQ and the M2 metabolite were utilized in the simulations where five interaction scenarios from strong inhibition (clearance fivefold decreased) to strong induction (clearance fivefold increased) were evaluated. In trial simulations, NCA systematically under-predicted the DDIs’ impact. The bias in average exposure was 29–96% for BDQ and 20–677% for M2. The model-based analysis generated unbiased predictions, and simultaneous fitting of metabolite data increased precision in DDI predictions. The discrepancy between the methods was also apparent for conducted trials, e.g., lopinavir/ritonavir was predicted to increased BDQ exposure 22% by NCA and 188% by model-based methods. In the design evaluation, studies with parallel designs were considered and shown to generally be inferior to sequential/cross-over designs. However, in the case of low inter-individual variability and no informative metabolite data, a prolonged parallel design could be favored. Model-based analysis for DDI assessments is preferable over NCA for victim drugs with a long half-life and should always be used when incomplete concentration-time profiles are part of the analysis.
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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.