Question

Hepatic Clearance Practice Problems PH4330 1. Normal CL value for this drug is 0.5 L/min and elimination is via the liver. V 100 L a. Is this a low, intermediate, or high E drug? b. In CHF (congestive heart failure) patient, Q is half the normal value of 800 ml/min. What would the hepatic clearance be in the CHF patient? What would be the normal and CHF FFp values? c. 2. Given the following pharmacokinetic information for a drug: .Q 1.5 liters per minute V 200 liters elimination is only by hepatic metabolism; binding in blood is 90% 4.0 hours .CLH-577.5 ml/min a. Predict the oral bioavailability of this drug; assume that bioavailability is b. s the elimination of this drug restricted or nonrestricted? reduced only by a hepatic first-pass mechanism. 3. What happens (increase, decrease, no change) to the following parameters as a result of a 50% reduction in hepatic blood flow? The drug normally has a hepatic clearance equal to 90% of hepatic blood flow and it is administered orally as a single dose. Use simplified equations if high or low E. The change must be greater than 25% to be considered a change. a. CLH b. E c. FFP

Answer 1

1. a) The ratio of the hepatic clearance of a drug to the hepatic blood flow is called the extraction ratio of the drug. Extraction ratio can be generally classified as high (>0.7), intermediate (0.3-0.7) or low (<0.3) according to the fraction of drug removed during one pass through the liver.

The extraction ratio of this drug is intermediate because it's clearance value is 0.5 .

b) Q is the hepatic blood flow ,in this case it is 400ml/min

Hepatic clearance in this case will be :-

Hepatic clearance = hepatic blood flow × efficiency of the liver to clear the drug from blood

Cl(h) = Q= 400ml/min