TABLE 1

Pharmacokinetic parameters used for clinical HDI predictions

ParametersValue
CA bioavailability (F)0.22a
MCA bioavailability (F)0.22b
CYP2A6 kdeg0.019–0.036 h−1
ka6c h−1
BP1c
CA fraction absorbed (Fa*Fg)0.46a
Systemic clearance (CL)44.826d l/h
Volume of distribution (Vss)381.475d l
MCA systemic clearance (CL)40.68 l/h
MCA volume of distribution (Vss)120.89 l
MCA fraction absorbed (Fa*Fg)0.46b
Nicotine fm,CYP2A60.77e
Letrozole fm,CYP2A60.8f
CA Ih,u (µM)12.21
MCA Ih,u (µM)14.39
  • a Obtained from rats and assumed to be the same in humans.

  • b Assumed to be the same as CA.

  • c Blood to plasma partition ratio is assumed.

  • d Calculated from rats using allometry (see Materials and Methods section).

  • e Benowitz and Jacob (1994).

  • f Estimated from Sioufi et al. (1997), Murai et al. (2009), and Chan et al. (2016).