Pharmacokinetic analysis
The BET pharmacokinetics was calculated based on the plasma concentration versus time using PhoenixWinNonLin software, version 6.3 (Certara, Princeton, New Jersey, USA), employing a noncompartmental analysis. Maximum plasma concentration (Cmax) and time to reach Cmax (Tmax) were obtained from data of the individual patients. Areas under the plasma concentration-time curves were calculated by the trapezoidal rule and extrapolated to the infinity. Apparent total clearance (CL/F) was evaluated by the equation CL/F = Dose/AUC0- and apparent volume of distribution (Vd/F) was calculated by the equation of the software. The BET placental transfer was evaluated by the umbilical cord to maternal vein concentration ratio and intervillous space to maternal vein concentration ratio.