Abstract:
PURPOSE:Drug transfer into milk is a general concern during lactation. Because data are limited in human subjects, particularly for new drugs, experimental animal models of lactational drug transfer are critical. This study analyzed drug transfer into milk in a mouse model, as well as the contribution of similar and dissimilar host factors. METHODS:Milk/plasma drug concentration ratios (M/P) in humans were obtained from the literature, while those in mice were determined experimentally after intraperitoneal implantation of osmotic pumps containing drugs of interest. Unbound drug fractions in plasma and milk were determined in vitro for both species. RESULTS:M/P values were determined for 27 drugs in mice and compared with those in human. These values were increased in mice for 21 drugs; the geometric mean ratio of M/P between mice and humans was 2.03 (95% CI, 1.42-2.89) for all 27 drugs. These results were reasonably explained by the relatively high protein and lipid content in mouse milk. Moreover, species-specific asymmetrical transport systems were suggested for 9 drugs. CONCLUSIONS:In addition to species-specific differences in milk protein and lipid content, variances in asymmetrical drug transport across the mammary epithelium may yield discordant M/P values in humans and mice.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Ito N,Ito K,Koshimichi H,Hisaka A,Honma M,Igarashi T,Suzuki Hdoi
10.1007/s11095-013-1085-5subject
Has Abstractpub_date
2013-09-01 00:00:00pages
2410-22issue
9eissn
0724-8741issn
1573-904Xjournal_volume
30pub_type
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journal_title:Pharmaceutical research
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