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Pharmacology

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General Pharmacology

Question
17 out of 91
 

Experiments shows that 95% of an oral 80-mg dose of verapamil is absorbed in a 70-kg test subject. However, because of extensive biotransformation during its first pass through the portal circulation, the Bio availability was only 0.25(25%). Assuming a liver blood flow of 1500mL/min, which of the following is the hepatic clearance of verapamil in this situation? (LQ)



A 60mL/min
B 375mL/min

C 740 mL/min
D 1110 mL/min

Ans. D 1110 mL/min

In this problem, the amount of verapamil entering the liver per unit time was 76 mg (80 mg x 0.95) and the amount leaving was 20 mg. Therefore,

76 mg-20 mg

ER = ------------------------------- = 0.74

76 mg

Clliver = (1500 mL/min) (0.74) = 1110 mL/min

a. With intravenous infusions of a drug, only the drug’s half-life determines how long it will take for blood levels to reach a steady state (on average, neither rising nor falling thereafter) so long as the infusion rate is not changed.

b. By definition, when steady state is reached, the amount of drug entering the blood per unit time is equal to the rate at which drug is being eliminated whether by excretion, metabolism, or a combination of both (depending on the drug).

c. The apparent volume of distribution has no impact on time to CSS Bioavailable does not, either, because with intravenous drug administration.

d. The bioavailability is 1.0 (100%). Clearance, a parameter that relates elimination rate of a drug to the drug’s concentration [Cl = rate of elimination (mg/h)/d concentration (mg/mL)]. Because clearance considers a rate of drug elimination, it affects the CSS but it is not a determinant of it.

e. The infusion rate clearly affects the blood concentration reached at steady state, but it does not affect the time needed to reach For example, if we had a drug with a half-life of 4 h, infused it at a rate of x mg/mm, and then repeated the experiment with the same drug at an infusion rate of 2x mg/mm, blood concentrations at steady state would clearly be different.

f. However, it would still take the same amount of time (roughly 4 to 5 half- lives), to reach steady state.

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