TABLE 5

Prediction of the in vivo BCRP ER of dantrolene in human based on the in vivo BCRP ER of dantrolene in preclinical species and BCRP expression at BBB

Species (Strain)BCRP Expression at BBBERin vivo of DantrolenePredicted Kp,uuaReference
fmol/μg⋅protein
Mouse (Friend virus B)3.53, 3.21 (mean 3.37)6.300.16Enokizono et al. (2008); Uchida et al. (2013);Agarwal et al. (2012)
Rat (Sprague Dawley)4.153.300.30Hoshi et al. (2013); Fuchs et al. (2014)
Human6.15, 8.14 (mean 7.15)9.1 (predicted)b0.10Shawahna et al. (2011); Uchida et al. (2011b)
  • a The Kp,uu value was predicted by the reciprocal of the ERin vivo value (eq. 6).

  • b The human ERin vivo value of dantrolene was predicted by (mean ERin vivo of dantrolene in mouse and rat −1) ÷ ratio of mean BCRP expression at mouse and rat to human BBB + 1. The BCRP transport capacity was assumed to be the same in human as mouse and rat.