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.
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.
Authors: J Wang; T Johnson; L Sahin; M S Tassinari; P O Anderson; T E Baker; C Bucci-Rechtweg; G J Burckart; C D Chambers; T W Hale; D Johnson-Lyles; R M Nelson; C Nguyen; D Pica-Branco; Z Ren; H Sachs; J Sauberan; A Zajicek; S Ito; L P Yao Journal: Clin Pharmacol Ther Date: 2017-06 Impact factor: 6.875
Authors: Ahizechukwu C Eke; Adeniyi Olagunju; Brookie M Best; Mark Mirochnick; Jeremiah D Momper; Elaine Abrams; Martina Penazzato; Tim R Cressey; Angela Colbers Journal: Clin Pharmacokinet Date: 2020-10 Impact factor: 6.447