کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8513410 | 1556495 | 2018 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Proof of Principle for Local Delivery of a c-Met Inhibitor
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
The reported proof of principle study demonstrated the feasibility of local delivery of a c-Met inhibitor (VXc-140) in a subcutaneous xenograft tumor model. VXc-140 was formulated in a wafer delivery system for direct implantation into the tumor. Systemic and local tumor exposure of VXc-140 was analyzed. High tumor exposures coupled with fast release of compound were associated with significant tumor regression and reduction in tumor levels of phosphorylated c-Met. High VXc-140 tumor-to-plasma ratios (â¼42 at the tumor periphery) were achieved. The tumor response achieved (7/11 partial response) with VXc-140 with the local delivery in the wafer (4 mg over 15 days) was comparable to the regression observed (11/15 partial response) for VXc-140 in the oral delivery (â¼8 mg total administered once a day for 2 weeks). Notably, the plasma levels in animals implanted with VXc-140 wafers ranged from 2 to 4 μM, which, although higher than trough levels achieved with oral administration, were well below oral Cmax levels (â¼42 μM) suggesting that toxicities associated with Cmax exposure may be reduced or eliminated by local delivery. The high tumor to plasma exposure of VXc-140 and the efficacy observed with local wafer delivery warrants further exploration into the utility of local delivery.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 107, Issue 3, March 2018, Pages 856-862
Journal: Journal of Pharmaceutical Sciences - Volume 107, Issue 3, March 2018, Pages 856-862
نویسندگان
Howard Li, Irina Kadiyala, Michael Briggs, Rebecca Shawgo, Karem Reda, Rima Patel, Kirk Tanner, Francoise Berlioz-Seux, Brinley Furey, Patricia Hurter, Diane M. Boucher,