Placental transfer, lacteal transfer and plasma protein binding of gemcitabine.

1. The placental transfer, lacteal transfer and plasma protein binding of gemcitabine have been studied in rat and dog after single intravenous administration of 10 mg/kg 14C-gemcitabine. 2. Radioactivity was distributed to the foetuses at 5 min after administration to rat on days 12 and 18 of gestation. The concentrations of radioactivity in the foetal liver, lung and kidney on day 18 of gestation were 4.0-6.4 times higher than in the maternal blood at 4 h after administration. Relatively high levels of radioactivity were noted in foetal tissues 24 h after administration, indicating slow elimination from the foetus. 3. The concentration of radioactivity in milk reached a maximum at 15 min after administration to the lactating rat on day 10 after delivery, then declined in a biphasic manner, and was below the detection limit at 48 h. The concentrations of radioactivity in milk were lower than plasma concentrations of radioactivity. 4. Plasma protein binding ratios were 10-16 and 1-7% between 5 min and 8 h after administration to the male rat and dog respectively. When fresh plasma from male rat, dog and adult man was spiked with 14C-gemcitabine at concentrations of 0.1-25 micrograms/ml, the plasma protein binding ratios were about 7% in both rat and dog, and 10% in man.