التفاصيل البيبلوغرافية
| العنوان: |
Local Transdermal Delivery of Telapristone Acetate Through Breast Skin, Compared With Oral Treatment: A Randomized Double‐Blind, Placebo‐Controlled Phase II Trial. |
| المؤلفون: |
Lee, Oukseub, Pilewskie, Melissa, Karlan, Scott, Tull, Mary B., Benante, Kelly, Xu, Yanfei, Blanco, Luis, Helenowski, Irene, Kocherginsky, Masha, Yadav, Shivangi, Hosseini, Omid, Hansen, Nora, Bethke, Kevin, Muzzio, Miguel, Troester, Melissa A., Dimond, Eileen, Perloff, Marjorie, Heckman‐Stoddard, Brandy, Khan, Seema A. |
| المصدر: |
Clinical Pharmacology & Therapeutics; Mar2021, Vol. 109 Issue 3, p728-738, 11p |
| مصطلحات موضوعية: |
SKIN permeability, TANDEM mass spectrometry, ACETATES, PROGESTERONE antagonists, CANCER prevention, LIQUID chromatography, PROGESTERONE receptors |
| مستخلص: |
Oral breast cancer prevention medications entail systemic exposure, limiting acceptance by high‐risk women. Delivery through the breast skin, although an attractive alternative, requires demonstration of drug distribution throughout the breast. We conducted a randomized double‐blind, placebo‐controlled phase II clinical trial comparing telapristone acetate, a progesterone receptor antagonist, administered orally (12 mg/day) or transdermally (12 mg/breast) for 4 ± 1 weeks to women planning mastectomy. Plasma and tissue concentrations, measured at five locations in the mastectomy specimen using liquid chromatography tandem mass spectrometry were compared. In 60 evaluable subjects, median drug concentration (ng/g tissue) was 103 (interquartile range (IQR): 46.3–336) in the oral vs. 2.82 (IQR: 1.4–5.5) in the transdermal group. Despite poor dermal permeation, within‐breast drug distribution pattern was identical in both groups (R2 = 0.88, P = 0.006), demonstrating that transdermally and orally delivered drug is distributed similarly through the breast, and is strongly influenced by tissue adiposity (P < 0.0001). Other skin‐penetrant drugs should be tested for breast cancer prevention. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
