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- Title
Prediction of Drug Transfer into Milk Considering Breast Cancer Resistance Protein (BCRP)-Mediated Transport.
- Authors
Ito, Naoki; Ito, Kousei; Ikebuchi, Yuki; Toyoda, Yu; Takada, Tappei; Hisaka, Akihiro; Oka, Akira; Suzuki, Hiroshi
- Abstract
Purpose: Drug transfer into milk is of concern due to the unnecessary exposure of infants to drugs. Proposed prediction methods for such transfer assume only passive drug diffusion across the mammary epithelium. This study reorganized data from the literature to assess the contribution of carrier-mediated transport to drug transfer into milk, and to improve the predictability thereof. Methods: Milk-to-plasma drug concentration ratios (M/Ps) in humans were exhaustively collected from the literature and converted into observed unbound concentration ratios (M/P). The ratios were also predicted based on passive diffusion across the mammary epithelium (M/P). An in vitro transport assay was performed for selected drugs in breast cancer resistance protein (BCRP)-expressing cell monolayers. Results: M/P and M/P values were compared for 166 drugs. M/P values were 1.5 times or more higher than M/P values for as many as 13 out of 16 known BCRP substrates, reconfirming BCRP as the predominant transporter contributing to secretory transfer of drugs into milk. Predictability of M/P values for selected BCRP substrates and non-substrates was improved by considering in vitro-evaluated BCRP-mediated transport relative to passive diffusion alone. Conclusions: The current analysis improved the predictability of drug transfer into milk, particularly for BCRP substrates, based on an exhaustive data overhaul followed by focused in vitro transport experimentation.
- Subjects
DRUG analysis; BREAST cancer treatment; LACTATION; IN vitro studies; EPITHELIUM; PHYSIOLOGY
- Publication
Pharmaceutical Research, 2015, Vol 32, Issue 8, p2527
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-015-1641-2