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HEPATIC EXTRACTION RATIO

 

Eg. Warfarin, Phenytoin.

Cl	=		Q x E
	..
	=	Q x	fu. Cl
			__________		Where Cl = intrinsic clearance of unbound drug
			Q + Fu.Cl
	..
		Q x	fu. Cl		(fu.Cl << Q)
			__________
			Q
	..
		fu x	Cl

fu (displacement), Cl

Ie. restrictive clearance.

When displacement occurs (fu ) : -

Cl and Vd

total levels

and free levels quickly return to initial values.

NB Patient now has:

- Lower total levels of drug.

- Increased fu and increased total clearance.

- No change in unbound clearance.

- t½ may , or as 

t½		0.693 x Vd
	=	__________
		Cl

- No change in free (active levels).

Clinical implications:

- No change in therapeutic response.

- Beware when monitoring total plasma levels (dose should not be increased).

 

 

HIGH HEPATIC EXTRACTION RATIO DRUGS

Eg. Propranolol, Lignocaine.

Cl	=	Q x	fu. Cl
			__________
			Q + Fu.Cl
	..
		Q x	fu. Cl		(fu.Cl >> Q)
			__________
			fu. Cl
	..
		Q

no change in Cl as fu 

Hence, changes in the protein binding of high hepatic clearance drugs could theoretically cause changes in free drug levels and therapeutic effect, but no clinically important example of this has yet been demonstrated.