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).