Citation

BibTex format

@article{Said:2026:10.1002/bcp.70806,
author = {Said, MM and de, Mooij RB and Jiao, D and Ovelgonne, RJ and Biram, R and Delgado-SanMartin, J and Rothman, AMK and Villar, SS and Roussakis, AA and Aman, J and Mathôt, RAA and Swart, EL and Wilkins, MR and Bartelink, IH},
doi = {10.1002/bcp.70806},
journal = {Br J Clin Pharmacol},
title = {Adaptive imatinib regimens can mitigate cumulative toxicity while sustaining hemodynamic benefit: A model-based simulation of the positioning imatinib for pulmonary arterial hypertension trial.},
url = {http://dx.doi.org/10.1002/bcp.70806},
year = {2026}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - AIMS: Imatinib improves hemodynamics in pulmonary arterial hypertension (PAH), but dose-dependent toxicity has limited its clinical development. We aimed to quantify the dose-efficacy-toxicity relationship and evaluate alternative dosing strategies using data from the PIPAH trial. METHODS: We analysed data from the Phase II PIPAH trial (17 enrolled; 15 contributed pharmacokinetic and safety data, 11 daily hemodynamic data). Total pulmonary resistance (TPR) was described using a turnover model and recurrent adverse events (AEs) using a repeated time-to-event model. RESULTS: Simulations showed that TPR reduction was dose-dependent (  E max   50%; E D 50   247 mg), whereas AE risk increased nonlinearly with dose ( E D 50   307 mg). Although a cumulative dose of 2400 mg produced similar TPR reductions, 300 mg once daily achieved a 20% reduction earlier than 200 mg (8 vs. 12 weeks) with only a modest increase in AE burden. CONCLUSIONS: Simulations support initiating treatment at 200 mg once daily with escalation to 300 mg after 8-12 weeks in patients who tolerate treatment.
AU  - Said,MM
AU  - de,Mooij RB
AU  - Jiao,D
AU  - Ovelgonne,RJ
AU  - Biram,R
AU  - Delgado-SanMartin,J
AU  - Rothman,AMK
AU  - Villar,SS
AU  - Roussakis,AA
AU  - Aman,J
AU  - Mathôt,RAA
AU  - Swart,EL
AU  - Wilkins,MR
AU  - Bartelink,IH
DO  - 10.1002/bcp.70806
PY  - 2026///
TI  - Adaptive imatinib regimens can mitigate cumulative toxicity while sustaining hemodynamic benefit: A model-based simulation of the positioning imatinib for pulmonary arterial hypertension trial.
T2  - Br J Clin Pharmacol
UR  - http://dx.doi.org/10.1002/bcp.70806
UR  - https://www.ncbi.nlm.nih.gov/pubmed/42692545
ER  -
Download