Pharmacokinetics

1. For a high extraction drug (e.g., metoprolol) administered IV to an elderly subject with reduced hepatic blood flow, which of the following is/are INCORRECT?
- Clearance of metoprolol stays the same because high extraction drugs behave like a low extraction drug when administered IV.
- Clearance of metoprolol stays the same because high extraction drugs behave like a high extraction drug when administered IV.
- a. Clearance of metoprolol is increased because the free fraction is increased.
- b. Clearance of metoprolol is increased because the free fraction is decreased.
- c. Clearance of metoprolol is decreased because the intrinsic clearance is decreased.
- d. Clearance of metoprolol is decreased because the intrinsic clearance is increased.

2. You are working in the ICU and have been asked to step down drug "X" from IV to oral formulation for an elderly patient. You gather from the literature that drug X is extensively metabolized, and that it can be given IV or PO. Examining the monograph, you noticed that drug X's IV dose is roughly equivalent to the oral dose, and that its oral bioavailability is relatively high. What would be the correct course of action? Select all correct answers.
- Roughly equivalent oral dose can be administered assuming drug X’s kinetics are likely similar in both routes of administration.
- You would double the dose because drug X is likely highly extracted by 1st pass metabolism to compensate for the IV to PO conversion.
- a. Drug X is likely a "low E" drug, hence you will need to consider reducing its oral dose as it is likely affected by patient’s reduced hepatic blood flow.
- b. Drug X is likely a "high E" drug, hence you will need to consider reducing its oral dose as it is likely affected by patient’s reduced hepatic blood flow.
- c. Drug X is likely a "low E" drug, hence you will need to monitor for changes in patient response when an enzyme inhibitor is administered at the same time.
- d. Drug X is likely a "high E" drug, hence you will need to monitor for changes in patient response when a protein binding displacement agent is administered at the same time.

3. Select all INCORRECT answers regarding the pharmacokinetics of an orally administered drug which is primarily cleared by glomerular filtration in the neonatal period.
- Clearance would be increased during the neonatal period due to increased glomerular filtration.
- Clearance would be decreased during the neonatal period due to decreased glomerular filtration.
- Clearance would be decreased during the neonatal period due to increased glomerular filtration and increased intrinsic clearance.
- Clearance would be increased during the neonatal period due to decreased intrinsic clearance.

Aminoglycosides

4. JN is a 33-year-old (dosing weight 84.1 kg) male who presents to the ER with a history of being bitten by a dog in the jaw 3 days ago. As a vet, the patient empirically started himself on amoxiclav BID. He now presents with a red, swollen mandible that is painful and warm to the touch. He also complains of fever and chills that started last night. He has no significant past medical history other than a documented severe allergy to cephalosporins. You are rounding with the infectious disease consultants and recommend starting clindamycin and gentamicin (170 mg IV Q8H) for antibiotic coverage.

5. Overnight, the patient’s status changed drastically. Due to unstable blood pressure and respiratory distress, he is transferred to the ICU. Cultures reveal gram (-) rods in the blood. Gentamicin serum concentrations drawn around the 3rd dose were:
- 4.2 mg/L (level taken at 0900 hr)
- 0.57 mg/L (level taken at 0725 hr)
- Gentamicin doses were given by intermittent IV infusion from 0800 to 0830

6. What is the elimination rate t1/2 in this patient in hours (provide to 3 significant figures)?

7. What is the gentamicin volume of distribution in liters (provide to 3 significant figures)?

8. What is the gentamicin clearance, in L/h (provide to 3 significant figures)?

9. The desired target peak is 9 mg/L (30 minutes after the end of the 30-minute infusion). What dose should be given every 8 hours to achieve the target peak? Round the dose to the nearest 5 mg.

10. The target trough should be no more than 1 mg/L. With your new dose, will the trough be less than 1 mg/L?
- No
- Yes