Cirrhosis

Impact of cirrhosis on drug exposure

substrate

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CYP metabolism is a minor pathway for the elimination of this drug. No relevant interaction with CYP inhibitors or inducers is expected.
Glucuronidation is a major pathway for the elimination of this drug. No relevant interaction with CYP inhibitors is expected. Some inducers (e.g. rifampicin) may lower its exposure.

substrate

Fraction metabolized by each CYP
Adults
Children
 
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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.