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Local Transdermal Delivery of Telapristone Acetate Through Breast Skin, Compared With Oral Treatment: A Randomized Double‐Blind, Placebo‐Controlled Phase II Trial
Author(s) -
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,
HeckmanStoddard Brandy,
Khan Seema A.
Publication year - 2021
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.2041
Subject(s) - transdermal , medicine , breast cancer , placebo , pharmacokinetics , interquartile range , randomized controlled trial , pharmacology , urology , cancer , pathology , alternative medicine
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 ( R 2 = 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.