A phase I study to assess the mass balance, excretion, and pharmacokinetics of [14C]-ixazomib, an oral proteasome inhibitor, in patients with advanced solid tumors
| العنوان: | A phase I study to assess the mass balance, excretion, and pharmacokinetics of [14C]-ixazomib, an oral proteasome inhibitor, in patients with advanced solid tumors |
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| المؤلفون: | Karthik Venkatakrishnan, Michael J. Hanley, Sandeepraj Pusalkar, Neeraj Gupta, Steven Zhang, Mihaela Plesescu, Xiaoquan Zhang, Bingxia Wang, Dale R. Shepard, Swapan Chowdhury, Cindy Q. Xia |
| المصدر: | Investigational New Drugs. 36:407-415 |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Pharmacology, Urine, 030226 pharmacology & pharmacy, Ixazomib, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Oncology, chemistry, Pharmacokinetics, Oral administration, 030220 oncology & carcinogenesis, Pharmacology (medical), Adverse effect, Feces, ADME |
| الوصف: | Summary This two-part, phase I study evaluated the mass balance, excretion, pharmacokinetics (PK), and safety of ixazomib in patients with advanced solid tumors. In Part A of the study, patients received a single 4.1 mg oral solution dose of [14C]-ixazomib containing ~500 nCi total radioactivity (TRA), followed by non-radiolabeled ixazomib (4 mg capsule) on days 14 and 21 of the 35-day PK cycle. Patients were confined to the clinic for the first 168 h post dose and returned for 24 h overnight clinic visits on days 14, 21, 28, and 35. Blood, urine, and fecal samples were collected during Part A to assess the mass balance (by accelerator mass spectrometry), excretion, and PK of ixazomib. During Part B of the study, patients received non-radiolabeled ixazomib (4 mg capsules) on days 1, 8, and 15 of 28-day cycles. After oral administration, ixazomib was rapidly absorbed with a median plasma Tmax of 0.5 h and represented 70% of total drug-related material in plasma. The mean total recovery of administered TRA was 83.9%; 62.1% in urine and 21.8% in feces. Only 3.23% of the administered dose was recovered in urine as unchanged drug up to 168 h post dose, suggesting that most of the TRA in urine was attributable to metabolites. All patients experienced a treatment-emergent adverse event, which most commonly involved the gastrointestinal system. These findings suggest that ixazomib is extensively metabolized, with urine representing the predominant route of excretion of drug-related material. Trial ID: ClinicalTrials.gov # NCT01953783. |
| تدمد: | 1573-0646 0167-6997 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::6f8e12a5907ce192f618e42bef8eb5de https://doi.org/10.1007/s10637-017-0509-1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........6f8e12a5907ce192f618e42bef8eb5de |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15730646 01676997 |
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