Trial reportClinical pharmacokinetics2015
Population pharmacokinetic-pharmacodynamic modelling of 24-h diastolic ambulatory blood pressure changes mediated by axitinib in patients with metastatic renal cell carcinoma.
Trial report in Clinical pharmacokinetics, 2015. 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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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.
- Exposure-response analyses of blood pressure and heart rate changes for methylphenidate in healthy adults.Journal of pharmacokinetics and pharmacodynamics · 2017Pooled it
- A Pharmacometric Framework for Axitinib Exposure, Efficacy, and Safety in Metastatic Renal Cell Carcinoma Patients.CPT: pharmacometrics & systems pharmacology · 2017Trial
- A Systematic Evaluation of the Dosing Regimens for Approved Targeted Therapies and Immune Checkpoint Inhibitors in Metastatic Renal Cell Carcinoma From a Project OPTIMUS Perspective.Journal of clinical pharmacology · 2025Review
- Optimization of blood pressure measurement practices for pharmacodynamic analyses of tyrosine-kinase inhibitors.Clinical and translational science · 2023Article
- A Profile of Avelumab Plus Axitinib in the Treatment of Renal Cell Carcinoma.Therapeutics and clinical risk management · 2022Review
- Absorption of the orally active multikinase inhibitor axitinib as a therapeutic index to guide dose titration in metastatic renal cell carcinoma.Investigational new drugs · 2021Article
- Pharmacodynamic analysis of hypertension caused by lenvatinib using real-world postmarketing surveillance data.CPT: pharmacometrics & systems pharmacology · 2021Article
- Quantifying the relationship between inhibition of VEGF receptor 2, drug-induced blood pressure elevation and hypertension.British journal of pharmacology · 2018Article
- Current Challenges of Cancer Anti-angiogenic Therapy and the Promise of Nanotherapeutics.Theranostics · 2018Review
- Axitinib in the treatment of renal cell carcinoma: design, development, and place in therapy.Drug design, development and therapy · 2017Review
- Review
- Axitinib plasma pharmacokinetics and ethnic differences.Investigational new drugs · 2015Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreased blood pressure (BP) is commonly observed in patients treated with vascular endothelial growth factor pathway inhibitors, including axitinib. Ambulatory BP monitoring (ABPM) and pharmacokinetic data were collected in a randomised, double-blind phase II study of axitinib with or without dose titration in previously untreated patients with metastatic renal cell carcinoma.
objectiveAims of these analyses were to (1) develop a population pharmacokinetic-pharmacodynamic model for describing the relationship between axitinib exposure and changes in diastolic BP (dBP) and (2) simulate changes in dBP with different axitinib dosing regimens.
methodsWe employed a three-stage modelling approach, which included development of (1) a baseline 24-h ABPM model, (2) a pharmacokinetic model from serial and sparse pharmacokinetic data, and (3) an indirect-response, maximum-effect (Emax) model to evaluate the exposure-driven effect of axitinib on dBP. Simulations (N = 1,000) were performed using the final pharmacokinetic-pharmacodynamic model to evaluate dBP changes on days 4 and 15 of treatment with different axitinib doses.
resultsBaseline ABPM data from 62 patients were best described by 24-h mean dBP and two cosine terms. The final indirect-response Emax model showed good agreement between observed 24-h ABPM data and population and individual predictions. The maximum increase in dBP was 20.8 %, and the axitinib concentration at which 50 % of the maximal increase in dBP was reached was 12.4 ng/mL.
conclusionOur model adequately describes the relationship between axitinib exposure and dBP increases. Results from these analyses may potentially be applied to infer dBP changes in patients administered axitinib at nonstandard doses.
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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.