Pharmacokinetics/Pharmacodynamics
hepatic enzyme metabolism; therefore, clearance is limited by hepatic enzymatic activity, and clearance is
independent of hepatic blood flow. Mathematically, this can be represented by:
fu × CLint<<<Q
According to this relationship, CLH can be simplified to:
CLH = fu × CLint
Again, the Css for hepatically metabolized drugs can be represented by the following equation:
Css = dose
CLH
where Css is the steady-state concentration and dose is the rate of drug input. Because CLH = fu × CLint for
low extraction ratio drugs, the equation can be modified to:
Css =
dose
fu × CLint
The unbound steady-state concentration for a low extraction ratio drug is represented by the following
equation:
Cssu = dose
CLint
drugs, altered CLint affects both the Css and the Cssu, whereas changes in the fu affect only the Css.
↔ Css
↔ Cssu
↑ Q
↓ Q
↑ CLint
↓ CLint
↑ fu
↓ fu
↔ Css
↔ Cssu
↓ Css
↓ Cssu
↑ Css
↑ Cssu
↓ Css
↔ Cssu
↑ Css
↔ Cssu
CLH = fu × CLint
| Css = | Dose |
|---|
fu × CLint
| Cssu = | Dose |
|---|
CLint
ratio drug.