ArticleBritish journal of clinical pharmacology2015
Integrated semi-physiological pharmacokinetic model for both sunitinib and its active metabolite SU12662.
Article in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Factors Affecting Pharmacokinetics of Sunitinib and Its Metabolite, SU12662: A Systematic Review of Population Pharmacokinetic Studies.European journal of drug metabolism and pharmacokinetics · 2025Pooled it
- Model-Informed Precision Dosing of Protein Kinase Inhibitors: Evaluation of Model-Averaging and Flattened Priors Methods.Clinical pharmacokinetics · 2026Trial
- Population Modeling Integrating Pharmacokinetics, Pharmacodynamics, Pharmacogenetics, and Clinical Outcome in Patients With Sunitinib-Treated Cancer.CPT: pharmacometrics & systems pharmacology · 2017Trial
- Development of Integrated Parent-Metabolite Pharmacokinetic Model With Apparent Presystemic Metabolism to Characterize the Disposition of Alverine.CPT: pharmacometrics & systems pharmacology · 2026Article
- Therapeutic Drug Monitoring and Model-Informed Precision Dosing of Oral TKIs and PARP Inhibitors: A Practical Framework for Clinical Implementation.Clinical pharmacokinetics · 2026Review
- Comparative Analysis of Traditional and Pharmacometric-Based Pharmacoeconomic Modeling in the Cost-Utility Evaluation of Sunitinib Therapy.PharmacoEconomics · 2025Article
- Pharmacokinetics of Enteral Lormetazepam in Mechanically Ventilated ICU Patients with COVID-19: An Adjunct Sedative Study.Clinical pharmacokinetics · 2024Article
- Physiologically-based pharmacokinetic models versus allometric scaling for prediction of tyrosine-kinase inhibitor exposure from adults to children.Cancer chemotherapy and pharmacology · 2024Article
- Semi-physiological Pharmacokinetic Model of Clozapine and Norclozapine in Healthy, Non-smoking Volunteers: The Impact of Race and Genetics.CNS drugs · 2024Article
- Integrating Clopidogrel's First-Pass Effect in a Joint Semi-Physiological Population Pharmacokinetic Model of the Drug and Its Inactive Carboxylic Acid Metabolite.Pharmaceutics · 2024Article
- Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Easy and reliable maximum a posteriori Bayesian estimation of pharmacokinetic parameters with the open-source R package mapbayr.CPT: pharmacometrics & systems pharmacology · 2021Article
- Imatinib, sunitinib and pazopanib: From flat-fixed dosing towards a pharmacokinetically guided personalized dose.British journal of clinical pharmacology · 2020Review
- Model-Based Biomarker Selection for Dose Individualization of Tyrosine-Kinase Inhibitors.Frontiers in pharmacology · 2020Article
- Drug-Induced Hypertension Caused by Multikinase Inhibitors (Sorafenib, Sunitinib, Lenvatinib and Axitinib) in Renal Cell Carcinoma Treatment.International journal of molecular sciences · 2019Review
- The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors.Oncotarget · 2017Article
- Practical Recommendations for Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology.Clinical pharmacology and therapeutics · 2017Review
- Optimizing the dose in cancer patients treated with imatinib, sunitinib and pazopanib.British journal of clinical pharmacology · 2017Article
- Development of a Pharmacokinetic Model to Describe the Complex Pharmacokinetics of Pazopanib in Cancer Patients.Clinical pharmacokinetics · 2017Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsPreviously published pharmacokinetic (PK) models for sunitinib and its active metabolite SU12662 were based on a limited dataset or lacked important elements such as correlations between sunitinib and its metabolite. The current study aimed to develop an improved PK model that circumvented these limitations and to prove the utility of the PK model in treatment optimization in clinical practice.
methodsOne thousand two hundred and five plasma samples from 70 cancer patients were collected from three PK studies with sunitinib and SU12662. A semi-physiological PK model for sunitinib and SU12662 was developed incorporating pre-systemic metabolism using non-linear mixed effects modelling (nonmem). Allometric scaling based on body weight was applied. The final model was used for simulation of the PK of different treatment regimens.
resultsSunitinib and SU12662 PK were best described by a one and two compartment model, respectively. Introduction of pre-systemic formation of SU12662 strongly improved model fit, compared with solely systemic metabolism. The clearance of sunitinib and SU12662 was estimated at 35.7 (relative standard error (RSE) 5.7%) l h(-1) and 17.1 (RSE 7.4%) l h(-1), respectively for 70 kg patients. Correlation coefficients were estimated between inter-individual variability of both clearances, both volumes of distribution and between clearance and volume of distribution of SU12662 as 0.53, 0.48 and 0.45, respectively. Simulation of the PK model predicted correctly the ratio of patients who did not reach proposed PK targets for efficacy.
conclusionsA semi-physiological PK model for sunitinib and SU12662 in cancer patients was presented including pre-systemic metabolism. The model was superior to previous PK models in many aspects.
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