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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Van Hasselt, J. G. C. Boekhout, A. H. Beijnen, J. H. Schellens, J. H. M. Huitema, A. D. R. |
| Description | Country affiliation: Netherlands Author Affiliation: van Hasselt JG ( Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. coenvanhasselt@gmail.com) |
| Abstract | Trastuzumab treatment is associated with cardiac dysfunction. The aim of this study was to develop a population pharmacokinetic-pharmacodynamic (PK-PD) model for the relationship between left ventricular ejection fraction (LVEF) and trastuzumab exposure and to identify associated clinically relevant covariates. Data from an unselected cohort of patients with early and advanced HER2-positive breast cancer receiving treatment with trastuzumab were analyzed using a nonlinear mixed-effects modeling approach. LVEF values from 240 patients were available. The data were best described by an effect-compartment model. The population LVEF recovery half-life after trastuzumab treatment (T(½rec)) was estimated at 49.7 days. The cumulative anthracycline dose was a significant determinant of the half maximal effect concentration (EC50), causing a 45.9% increase in sensitivity (decrease in EC50) at the maximum cumulative anthracycline dose. The developed population PK-PD model may be used to establish optimal treatment and cardiac monitoring strategies for trastuzumab. |
| File Format | HTM / HTML |
| ISSN | 00099236 |
| Issue Number | 1 |
| Volume Number | 90 |
| e-ISSN | 15326535 |
| Journal | Clinical Pharmacology & Therapeutics |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2011-07-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Pharmacology Antibodies, Monoclonal Adverse Effects Pharmacokinetics Antineoplastic Agents Heart Diseases Chemically Induced Epidemiology Adult Aged Algorithms Anthracyclines Administration & Dosage Antibodies, Monoclonal, Humanized Breast Neoplasms Drug Therapy Metabolism Data Interpretation, Statistical Drug Interactions Female Genes, Erbb-2 Genetics Guidelines As Topic Half-life Humans Middle Aged Models, Statistical Population Prospective Studies Reproducibility Of Results Stroke Volume Drug Effects Taxoids Trastuzumab Ventricular Function, Left Journal Article |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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