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10. It was determined that 95% of an oral 80-mg dose of verapamil was absorbed in a 70-kg test subject. However, because of extensive biotransformation during its first pass through the portal circulation, the bioavailability of verapamil was only 25%. Assuming a liver blood flow of 1500 mL/min,
the hepatic clearance of verapamil in this situation was
a. 60 mL/min
b. 375 mL/min
c. 740 mL/min
d. 1110 mL/min
e. 1425 mL/min
22 Pharmacology
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hi zkadhem cud u please answer thgis
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please explain the calculation?
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10. The answer is d.
Bioavailability is defined as the fraction or percentage of a drug that becomes available to the systemic circulation following administration by any route. This takes into consideration that not all of an orally administered drug is absorbed and that a drug can be removed from the plasma and biotransformed by the liver during its initial passage through the portal circulation. A bioavailability of 25% indicates that only 20 mg of the 80-mg dose (i.e., 80 mg × 0.25 = 20 mg) reached the systemic circulation.Organ clearance can be determined by knowing the blood flow through the organ (Q) and the extraction ratio (ER) for the drug by the organ, according to the equation
CLorgan = Q × ER
The extraction ratio is dependent upon the amounts of drug entering (Ci)
and exiting (Co) the organ:
ER =Ci *Co/Ci
In this problem, the amount of verapamil entering the liver was 76 mg
(80 mg × 0.95) and the amount leaving was 20 mg. Therefore,
ER = 0.74
CLliver = (1500 mL/min) (0.74) = 1110 mL/min
76 mg − 20 mg
76 mg
Ci × Co
Ci
