Hepatic Clearance Calculations

A. A solution Verapamil is administered to the portal vein of the isolated perfused liver of a rat at a concentration of 8.6 mg/L. After 5 minutes, the concentration that is measured at the hepatic vein is 1.55 mg/L. What is the hepatic extraction rate (ERH) of verapamil in this model?

B. If Verapamil is given to a patient with a hepatic blood flow of 730 mL/min. Calculate the hepatic clearance of verapamil assuming that the only clearance mechanism for this drug is hepatic and that this drug does not bind to plasma proteins. Consider the ERH calculated for the rat model above to be equivalent to the ERH in humans.

C. A 35 year old patient checks into the hospital with the diagnosis of acute asthma attack. The physician decides to prescribe a new drug anti-asthmatic drug called Wheezenomor. The drug is infused into the patient at a rate of 14.4 mg/min to address the acute asthma attack. The patient appears healthy otherwise and laboratory tests reports a hepatic blood flow of 1090 mL/min and an intrinsic hepatic clearance of 12870 mL/min. The manufacturer of Wheezenomore, describes this drug as not binding to plasma proteins and that it is eliminated completely via hepatic metabolism. Calculate the hepatic clearance and the concentration of this drug at steady state (in mg/L).

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Some Equations:

Hepatic Extraction Ratio (ER<sub>H</sub>)
Equation 17.3.1 Hepatic Extraction Ratio (ERH)

Steady State Concentration Cp<sub>ss</sub>
Equation 17.3.2 Steady State Concentration (Cpss)

Questions provided by Lucila Garcia-Contreras. Ph.D.
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