TABLE 5

GA-dependent changes in the fetal metabolic (CLf0) and placental efflux (CLPM) clearances of drugs X and Y

Drug X ClearanceDrug Y Clearance
GA Week 20GA Week 40Week 40/Week 20 RatioGA Week 20GA Week 40Week 40/Week 20 Ratio
l/h
CLPDa0.211.808.62.222.59.
CLf00.11 (53% of CLPD)0.90 (50% of CLPD)8.200N/A
CLPMb (P-gp mediated)0.70c (330% of CLPD)0.36 (20% of CLPD)0.517.4 (336% of CLPD)4.5 (20% of CLPD)0.6
  • a Denotes transplacental passive diffusion clearance after accounting for binding.

  • b Denotes efflux clearance mediated by P-gp located on the apical side of placenta; assumed to be 20% of CLPD at week 40.

  • c Back-extrapolated based on the assumed 5-fold decrease in placental P-gp expression and the reported 2.6-fold increase in the placenta volume (Abduljalil et al., 2012).