Pharmacokinetic analysis
The BET pharmacokinetics was calculated based on the plasma
concentration versus time using PhoenixⓇWinNonLinⓇ 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.