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How fast will the liver clear this drug?

Liver microsome CLint to hepatic clearance (CLh) calculator

Predicts how fast the human liver removes a drug (hepatic clearance, CLh) from its half-life in liver microsomes, the enzyme-rich fraction of liver tissue.

When to use itUse it during candidate selection, to spot early the compounds the liver breaks down too fast for the effect to last.

Prefilled with an example: a drug that falls to half in 20 minutes in liver microsomes. Change any value and the result updates.

min

The time for the drug to fall to half when incubated with liver microsomes.

µL

The total volume of the reaction mixture in the assay.

mg

The amount of microsomal protein. Concentrations of 0.2 to 0.5 mg/mL are common.

mg/g liver

About 32 is used for humans (reported range 26 to 54).

g liver/kg

Roughly 20 to 26 g in adults.

0–1

Corrects for drug bound to the microsomes. Leave at 1 if unknown.

0–1

The share of drug free to move in the blood. Leave at 1 if unknown.

mL/min/kg

About 20.7 mL/min/kg in humans.

Predicted hepatic clearance (CLh)14.33 mL/min/kg
In vitro intrinsic clearance (CLint, in vitro)69.3 µL/min/mg
Scaled to the whole liver (CLint, scaled)46.57 mL/min/kg
Corrected for binding (CLint,u)46.57 mL/min/kg

Clearance (CLh about 14.33 mL/min/kg) depends on both hepatic blood flow and enzyme activity. Taken orally, about 69.23% would be metabolized on its first pass through the liver.

What limits the clearance

The row that matches your result is marked.

  • Corrected enzyme capacity (fu,B × CLint,u) at least 5 times hepatic blood flowFlow-limited (CLh approaches hepatic blood flow)Almost all drug reaching the liver is metabolized. Clearance cannot exceed the blood flow into the liver.
  • Corrected enzyme capacity at most 0.2 times hepatic blood flowLimited by enzymes and protein bindingOnly part of the drug is metabolized on each pass. Clearance depends on enzyme activity and on how strongly the drug binds to blood proteins.
  • In between (0.2 to 5 times)Your resultFlow, enzymes and binding all matterAn intermediate range where no single factor decides.
  • In every caseExcludes elimination outside the liverConsider renal excretion and other routes separately. This calculator predicts only elimination by hepatic metabolism.

How it is calculated

The in vitro rate of metabolism (CLint, in vitro) is scaled up to the whole liver and corrected for binding, then converted to hepatic clearance with a model that accounts for liver blood flow (the well-stirred model). The results also list the intermediate values.

CLint,invitro = 0.693/t1/2 × (incubation volume/protein) → × MPPGL × liver weight/1000 = CLint,scaled → ÷ fu,inc = CLint,u → CLh = QH·fu,B·CLint,u / (QH + fu,B·CLint,u)

Source: In vitro clearance is scaled to the whole liver and converted to hepatic clearance with the well-stirred model (Obach RS 1999, and the scaling approach of Houston JB and colleagues).

With your numbers

  1. CLint(in vitro) = (0.693 ÷ t½) × (incubation volume ÷ protein) = (0.693 ÷ 20) × (1,000 ÷ 0.5) = 69.3 µL/min/mg
  2. CLint(scaled) = CLint × MPPGL × liver weight ÷ 1000 = 46.57 mL/min/kg
  3. CLint,u = scaled ÷ fu(inc) = 46.57 ÷ 1 = 46.57 mL/min/kg
  4. CLh = (QH × fu_B × CLint,u) ÷ (QH + fu_B × CLint,u) = 14.33 mL/min/kg (well-stirred)
  5. hepatic extraction ratio E = CLh ÷ QH = 14.33 ÷ 20.7 = 0.6923

Limits of this calculation

  • Predicting in vivo values from in vitro data (IVIVE) depends heavily on assumptions such as MPPGL, liver weight, blood flow and binding corrections, and can differ from observed clearance.
  • Only elimination by hepatic metabolism is predicted. Renal excretion and metabolism outside the liver are not included.
  • Leaving fu,inc and fu,B at 1 tends to overestimate clearance for highly protein-bound drugs. Treat the result as an estimate for learning.

Primary sources

Every calculator gives an estimate for learning, built on published information and primary sources. Real decisions follow the applicable guidance and expert judgment.