title: Contribution of protein binding, lipid partitioning, and asymmetrical transport to drug transfer into milk in mouse versus human.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pediatrics, The University of Tokyo Hospital Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ito
authors.forename: Kousei
authors.initials: K
authors.lastname: Ito
authors.forename: Hiroki
authors.initials: H
authors.lastname: Koshimichi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hisaka
authors.forename: Masashi
authors.initials: M
authors.lastname: Honma
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008892:Milk / Q000378:metabolism*; D008894:Milk Proteins / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000097:blood* / Q000378:metabolism*; D010599:Pharmacokinetics; D011485:Protein Binding
chemical_list: D001798:Blood Proteins; D008894:Milk Proteins; D004364:Pharmaceutical Preparations