Pharmacokinetics (Multiple choice and short answer questions)

*Please answer these questions only if you know this topic thoroughly and show all calculations*

ALL QUESTIONS RELATED TO THE DRUG TORANDOLIN

In the market, the chief competitior of a drug named Mirandolin is made by another company and is called Torandolin.

The average blood AUC of Torandolin after a 50 mg iv bolus dose is 0.575 mg x h/L given to healthy volunteers.

According to published studies, Torandolin is completely cleared by hepatic metabolism.

Like Mirandolin, Torandolin is extensively bound in blood

Torandolin is nearly completely absorbed after oral tablets (fg = 1)

1) What is the CL of Torandolin in healthy volunteers, in L/h. Provide to 3 sinificant figures. (1 pt)

2) What is the hepatic extraction ratio of Torandolin in healthy subjects? Provide to 3 significant figure (1 pt)

Phenobarbital induces the metabolism of Torandolin (increases CL(prime)int by a factor of 2).

3) After a 50 mg iv dose, what would be the expected effect on the total Torandolin AUC if phenobarbital was administered (compared to Torandolin alone)? (1 pt)

Lower Torandolin AUC by a factor of 2 (with phenobarbital)

No difference in AUC

Higher Torandolin AUC by a factor of 2 (with phenobarbital)

4) With phenobarbital, what Torandolin dose would have to be given orally to achieve the same overall level of effect as a 500 mg oral Torandolin dose alone? (1 pt)

125 mg

250 mg

500 mg

1000 mg

2000 mg

In congestive heart failure (CHF), hepatic blood flow (Q) is decreased by a factor of 2 (from 90 to 45 L/h)

5) After an iv dose of Torandolin, what would be the expected effect of CHF on the total AUC (measured using a typical assay method)?

Decreased AUC by a factor of 2 with CHF

No change in AUC with CHF

Increased AUC by a factor of 2 with CHF

6) With CHF, what Torandolin dose would have to be given orally to achieve the same overall level of effect as a 500 mg oral Torandolin dose to a healthy volunteer?

125 mg

250 mg

500 mg

1000 mg

2000 mg

7) Cimetidine displaces Torandolin from plasma proteins and increases the fu, blood by 2-fold. After a 50 mg iv dose, what would be the expected effect on the total Torandolin AUC in blood if cimetidine was co-administered (compared to Torandolin alone)?

Lower Torandolin AUC by a factor of 2 (with cimetidine)

No difference in AUC

Higher Torandolin AUC by a factor of 2 (with cimetidine)

8) With cimetidine, what Torandolin dose would have to be given orally to achieve the same overall level of effect as a 500 mg oral Torandolin dose to a healthy volunteer?

125 mg

250 mg

500 mg

1000 mg

2000 mg

9) Torandolin has an unbound fraction in blood of 0.05. This means it must have a Vdss that is:

Very low, close to blood volume

Very high, much greater than total body mass

Cannot tell with the given information

Upon further investigation, the company marketing Torandolin finds that its main metabolite (M1) has as much activity and a longer terminal-phase half-life than Torandolin after IV doses.

10) What would be an advantage of a longer half-life with repeated doses?

The ability to give fewer doses per day

The ability to maintain reduced fluctuation between steady-state peaks and troughs

The ability to achieve a faster rate of absorption (increase in ka)

A reduced distribution to tissues