دورية أكاديمية
Creation of Novel Sensitive Probe Substrate and Moderate Inhibitor Models for a Comprehensive Prediction of CYP2C8 Interactions for Tucatinib.
| العنوان: | Creation of Novel Sensitive Probe Substrate and Moderate Inhibitor Models for a Comprehensive Prediction of CYP2C8 Interactions for Tucatinib. |
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| المؤلفون: | Templeton IE; Certara, UK Ltd. (Simcyp Division), Sheffield, UK., Rowland-Yeo K; Certara, UK Ltd. (Simcyp Division), Sheffield, UK., Jones HM; Certara, UK Ltd. (Simcyp Division), Sheffield, UK., Endres CJ; Quantitative Pharmacology and Disposition, Seagen Inc., Bothell, Washington, USA., Topletz-Erickson AR; Quantitative Pharmacology and Disposition, Seagen Inc., Bothell, Washington, USA., Sun H; Quantitative Pharmacology and Disposition, Seagen Inc., Bothell, Washington, USA., Lee AJ; Quantitative Pharmacology and Disposition, Seagen Inc., Bothell, Washington, USA. |
| المصدر: | Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2024 Feb; Vol. 115 (2), pp. 299-308. Date of Electronic Publication: 2023 Dec 08. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley Country of Publication: United States NLM ID: 0372741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-6535 (Electronic) Linking ISSN: 00099236 NLM ISO Abbreviation: Clin Pharmacol Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2015- : Hoboken, NJ : Wiley Original Publication: St. Louis : C.V. Mosby |
| مواضيع طبية MeSH: | Gemfibrozil*/pharmacokinetics , Cytochrome P-450 CYP2C8 Inhibitors* , Oxazoles* , Pyridines* , Quinazolines*, Humans ; Cytochrome P-450 CYP3A ; Cytochrome P-450 CYP2C8 ; Cytochrome P-450 CYP2C9 ; Drug Interactions ; Models, Biological ; Cytochrome P-450 CYP3A Inhibitors |
| مستخلص: | A physiologically-based pharmacokinetic (PBPK) model was developed to simulate plasma concentrations of tucatinib (TUKYSA®) after single-dose or multiple-dose administration of 300 mg b.i.d. orally. This PBPK model was subsequently applied to support evaluation of drug-drug interaction (DDI) risk as a perpetrator resulting from tucatinib inhibition of CYP3A4, CYP2C8, CYP2C9, P-gp, or MATE1/2-K. The PBPK model was also applied to support evaluation of DDI risk as a victim resulting from co-administration with CYP3A4 or CYP2C8 inhibitors, or a CYP3A4 inducer. After refinement with clinical DDI data, the final PBPK model was able to recover the clinically observed single and multiple-dose plasma concentrations for tucatinib when tucatinib was administered as a single agent in healthy subjects. In addition, the final model was able to recover clinically observed plasma concentrations of tucatinib when administered in combination with itraconazole, rifampin, or gemfibrozil as well as clinically observed plasma concentrations of probe substrates of CYP3A4, CYP2C8, CYP2C9, P-gp, or MATE1/2-K. The PBPK model was then applied to prospectively predict the potential perpetrator or victim DDIs with other substrates, inducers, or inhibitors. To simulate a potential interaction with a moderate CYP2C8 inhibitor, two novel PBPK models representing a moderate CYP2C8 inhibitor and a sensitive CYP2C8 substrate were developed based on the existing PBPK models for gemfibrozil and rosiglitazone, respectively. The simulated population geometric mean area under the curve ratio of tucatinib with a moderate CYP2C8 inhibitor ranged from 1.98- to 3.08-fold, and based on these results, no dose modifications were proposed for moderate CYP2C8 inhibitors for the tucatinib label. (© 2023 Seagen Inc. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.) |
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| معلومات مُعتمدة: | Seagen Inc. |
| المشرفين على المادة: | 234248D0HH (tucatinib) Q8X02027X3 (Gemfibrozil) 0 (Cytochrome P-450 CYP2C8 Inhibitors) EC 1.14.14.1 (Cytochrome P-450 CYP3A) EC 1.14.14.1 (Cytochrome P-450 CYP2C8) EC 1.14.13.- (Cytochrome P-450 CYP2C9) 0 (Cytochrome P-450 CYP3A Inhibitors) EC 1.14.14.1 (CYP2C8 protein, human) 0 (Oxazoles) 0 (Pyridines) 0 (Quinazolines) |
| تواريخ الأحداث: | Date Created: 20231116 Date Completed: 20240123 Latest Revision: 20240411 |
| رمز التحديث: | 20240412 |
| DOI: | 10.1002/cpt.3104 |
| PMID: | 37971208 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1532-6535 |
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| DOI: | 10.1002/cpt.3104 |