Prediction of systemic exposure
A multivariate stepwise linear regression analysis revealed that sex,
weight, total bilirubin, platelet count and H/L ratio affected the
exposure of propranolol. A subject with normal liver function was
excluded in this model development due to his markedly high
Cmax and AUClast: Cmaxand AUClast of that subject were higher than the mean
Cmax and mean AUClast of other normal
subjects by 6.7 folds and 6.8 folds, respectively.
Male sex decreased both Cmax and AUClastand the increase of weight also reduced both parameters. The
Cmax and AUClast were increased by 6.155
ng/mL and 26.372 ng·h/mL, respectively for every 1 mg/dL increase in
total bilirubin and they were increased by 35.328 ng/mL and 176.745
ng·h/mL, respectively as H/L ratio increase by 1. Platelet count
influenced on AUClast but not on Cmax.
By the regression analysis, the equation that best predicts
Cmax and AUClast were as follows:
Cmax (ng/mL) = 50.976 - 18.743×sex[M:1;F:0] -
0.408×weight + 6.155×total bilirubin + 35.328×H/L ratio (adjusted
r2=0.440), AUClast (ng·h/mL) = 298.86
– 71.080×sex[M:1;F:0] – 2.158×weight – 0.312×platelet count
+26.372×total bilirubin + 176.745×H/L ratio (adjusted
r2=0.500).