Placental Transfer and Pharmacokinetics of a Single Oral Dose of the Fluoroquinolone Antibacterial DW-116 in Rats

The present study was conducted to investigate the placental transfer and pharmacokinetics of the flu-oroquinolone antibacterial DW-116 in pregnant rats. The placental transfer and pharmacokinetics of DW-116 were examined after a single oral dose of 500 mg $^{14}C$ DW-116/kg on gestational day 18. Maternal and fetal tissues were collected at 0.17 0.5,1,2,4,8, and 24 h after dosing. Maximum radioactivity was detected in maternal plasma, placenta, and whole fetus at 1 h, and in amniotic plasma at 4 h after dosing. Thereafter, radioactivity gradually disappeared from these tissues and was 16~28% of maximum levels at 24 h after dosing. Radioactivity in whole fetus were higher than those in the maternal plasma and placenta. The $T_{1/2,abs}$, $T_{1/2,{\beta}},$ AUC, $T_{max},$ and $C_{max}$ in the maternal plasma were approximately 6 min, 13.3 h, 1620 $ug^*hr/ml,$ 0.5 h, and 136 ug/ml, respectively. Those in the placenta were approximately 20 min, 12.3 h, 2150 $ug^*h/$m\ell$,$ 1.0 h, and 172 ug/ml, respectively. Those in the whole fetus were 13 min, 12.8 h,2549 $ug^*h/$m\ell$,$ 1 h, and 191 ug/ml, respectively. In the amniotic fluid of maternal uterus, the 4T_1/2,abs}$, $T1/2,{\beta},$ AUC, $T_{max},$ and $C_{max}$ were approximately 1.3 h,9.3 h,2508 $ug^*h/$m\ell$,$ 4.4 h, and 135 ug/ml, respectively. While DW-116 disappeared biphasically from maternal plasma, whole fetus and placenta, it was eliminated monophasically from amniotic fluid. In conclusion, this study demonstrated that the absorption and distribution of DW-116 in maternal plasma and placenta were extensively rapid, and that the test chemical well passed the blood-placenta barrier and was transferred to the fetus.

랫드에서 fluoroquinolone 항균제 DW-116의 단회 경구투여에 의한 태반통과와 약물동태연구