Cirrhosis

Impact of cirrhosis on drug exposure

substrate

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substrate

Fraction metabolized by each CYP
Adults
Children

Route

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Route

 

Parameters

  Fraction of activity remaining Drug unbound fraction Drug intestinal bioavailability
Child Pugh Class fupCIR/fup FgCIR/Fg
 

AUC ratios

Child-Pugh Class
 
Show AUC ratios' interindividual distribution (5th to 95th percentiles)
 
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Definitions

AUCuCIR
Unbound AUC of the substrate in a cirrhotic patient over the dosing interval at steady-state.
AUCu
Unbound Area Under the substrate Concentration in a non-cirrhotic patient over the dosing interval at steady-state.
AUCuCIR / AUCu
This ratio is useful for adapting the initial dose of the substrate to be given to a cirrhotic patient.
AUCCIR
AUC of the substrate in a cirrhotic patient over the dosing interval at steady-state.
AUC
Area Under the substrate Concentration in a non-cirrhotic patient over the dosing interval at steady-state.
AUCCIR / AUC
This ratio is useful to compare predicted vs observed data, because measurements are usually based on total rather than unbound concentrations.