Nakanomyo H, Ishikawa K, Esumi Y, Takaichi M, Jin Y, Gunji S, Ishikawa H, Sonobe J
Preclinical Research Laboratories, Bristol-Myers Research Institute, Ltd.
Jpn J Antibiot. 1990 Jul;43(7):1325-34.
Studies were done in rats on placental transfer and excretion into milk of 14C-BMY-28100 upon single oral administration. Studies on absorption, distribution and excretion of 14C-BMY-28100 were also done upon multiple dosing. 1. Fetal tissue concentration of the drug reached a maximum at 6 hours after dosing on day 18 of gestation. The highest concentration observed was only 0.56 microgram equiv./g in fetal kidney; The transfer of radioactivity into the fetus was low. Similar results were obtained from whole body autoradiograms performed in rats on day 12 and day 18 of gestation. 2. Concentrations of radioactivity in milk reached a maximum of 0.60 microgram equiv./ml at 1 hour after administration, and gradually decreased thereafter. The maximum concentration in milk was 10% of the plasma concentration measured at the same time. 3. In the multiple oral administration study, 24 hours blood levels of radioactivity rose progressively with each dose, and reached a level 3.8 times higher than that observed with single dosing by the final (21st) administration. Tissue concentrations were relatively high in aorta, kidney and large intestine as were found upon single administration. However, the ratios of these levels between multiple and single dosing were lower than those observed in blood; 1.7, 3.6 and 2.9 for aorta, kidney and large intestine, respectively. Urinary and fecal excretion were constant after the 2nd administration.
对大鼠进行了研究，以观察单次口服14C - BMY - 28100后其在胎盘的转运及向乳汁中的排泄情况。还进行了多次给药后14C - BMY - 28100的吸收、分布和排泄研究。1. 在妊娠第18天给药后6小时，胎儿组织中的药物浓度达到最高。在胎儿肾脏中观察到的最高浓度仅为0.56微克当量/克；放射性物质向胎儿的转运较低。在妊娠第12天和第18天对大鼠进行的全身放射自显影也得到了类似结果。2. 给药后1小时，乳汁中的放射性浓度最高达到0.60微克当量/毫升，此后逐渐下降。乳汁中的最高浓度是同一时间测得的血浆浓度的10%。3. 在多次口服给药研究中，每次给药后24小时的放射性血药浓度逐渐升高，在最后一次（第21次）给药时达到比单次给药时观察到的水平高3.8倍的水平。与单次给药时一样，主动脉、肾脏和大肠中的组织浓度相对较高。然而，多次给药与单次给药时这些组织浓度的比值低于血液中的比值；主动脉、肾脏和大肠的比值分别为1.7、3.6和2.9。第二次给药后，尿液和粪便排泄量保持恒定。
