Hepatic Clearance Calculation Formula

Majority of drugs are metabolized by the liver. But a few of drugs need individualized dosing based on liver function. In this article we share the hepatic clearance calculation formula and drug dose adjustment way for hepatic failure.

Although  measurements  of  the  creatinine clearance level can be used for dose adjustments in cases  of  impaired  renal  function,  there  is  no naturally  occurring  substance  that can  be  used  to estimate the  hepatic clearance  of  drugs. The Child-Pugh score is composed of several clinical variables and is used widely for the assessment of prognosis in patients with liver cirrhosis.

The  following  equation  may  be  used  to measure  the  hepatic  clearance (Clh)  of  a  drug  after assessing changing in blood flow and intrinsic Clint.

Clh = (Q×Clint)/(Q+Clint) 

Alternatively, hepatic drug clearance (CLH), defined as the volume of blood from which drug is removed completely by the liver per unit time, is a function of hepatic blood flow (QH) and the hepatic extraction ratio (EH) of the drug.


Since EH depends on liver blood flow, the intrinsic clearance of unbound drug (CLint), and the fraction of unbound drug in blood (fu), the following fundamental equation for CLH has been derived:

This equation is based on the “well-stirred” or “venous equilibration” model, a kinetic model used most frequently to describe the relationship between hepatic drug clearance and the three primary determinants of hepatic drug elimination, i.e., blood flow, drug binding in blood, and the intrinsic clearance.

Read also: Creatinine Clearance Calculation Formula

Dose Adjustment in Hepatic Failure

For each drug case, the physician need to assesses the degree of hepatic impairment and consider the known pharmacokinetics and pharmacodynamics of the drug.

Starting therapy with small doses and plasma level monitoring provides the best opportunity for safe and efficacious treatment.

For severe liver dysfunction (albumin < 30 g/L; INR > 1.2):

  • If the drug is a high clearance drug (liver blood flow dependent) reduce dose by 50% (e.g., Opioids, SSRIs etc.)
  • If the drug is a low clearance drug (flow in-dependent) reduce dose by 25% (e.g.: Paracetamol, NSAIDs etc.)

Note: INR = International Normalized Ratio

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