Pharmacokinetics

Protein binding

Protein binding A certain drug is 80% protein bound. Another drug is given that decreases the protein binding to 60%. Which of the following would change? A. Loading dose B. Maintenance dose C. Half life D. AUC, unbound E. None of the above E

Protein binding Which of the following do NOT affect the half life of a drug? A. fut B. fup C. CLu D. Vt Which of the following MUST change for you to change the LD? A. CLu C. fut Which of the following MUST change for you to change the MD?* B C A

Protein binding What type of drugs does albumin bind? A. Acidic B. Basic What type of drugs does AAG1 bind? Which type of protein has high capacity, but low affinity? A. Transcortin B. Albumin C. Thyroid binding globulin D. A and C Which type of protein has low capacity, but high affinity? A B D

Protein binding A drug is 75% protein bound with a therapeutic range of 10 to 20 mg/L. Calculate the unbound, therapeutic range of the drug. When are can you simplify this formula? A. When the drug is bound to a high capacity, low affinity protein such as albumin B. When the drug is bound to a low capacity, high affinity protein such as transcortin C. When 1/Ka>>Cu D. When 1/Ka<<Cu E. A and C 2.5 to 5 E

Protein binding When you do simplify the formula, what are you saying? A. fu is only affected by N and Ka B. Cu affects fu C. fu and Cu are independent D. A and C If you have a protein that tends to become saturated with a drug, what does this mean? D B

Protein binding For a drug that primarily binds albumin, what happens to fup if you increase Ka? A. Increase fu B. Decrease fu C. Nothing, they are independent For a drug that primarily binds albumin, what happens to fup if you decrease Cu? B C

Protein binding Prednisone binds transcortin and albumin, while methylprednisolone only binds to albumin. How does the fu for each drug change with increasing plasma concentration? A. Fu, prednisone is the SAME, fu, methylpred INCREASES B. fu, prednisone INCREASES, fu, methylpred is the SAME C. fu, pred INCREASES, fu, methylpred DECREASES D. fu, pred is the SAME, fu, methylpred is the SAME Based on the answer, what happens to: CL CL,u Vss Vss,u t1/2 B 6.1 recitation

Protein binding A drug is able to displace two drugs: Drug A (fup=0.001) and Drug B (fup=0.5). Which drug interaction has the biggest therapeutic impact? A. Drug A B. Drug B If fut >> fup, what does this mean? A. Volume of distribution is very low B. Volume of distribution is very high C. Neither, unable to tell from this information A

Protein binding What should you look at to determine the volume of distribution? A. fup B. fut C. Neither D. Ratio of fup and fut D

Protein binding In the aspirin phenytoin example, aspirin increased the fup of phenytoin. Why was the LD not changed? In the aspirin phenytoin example, aspirin increase the fup of phenytoin. Why was the MD not changed? If fu increases, what happens to Clu? CL? What is CLu a measure of? Vss,u was not affected CL,u was not affected Nothing happens to CLu—they are independent. If increase fu, increase CL Clu is a measure of innate metabolic activity.

Protein binding A CKD receiving phenytoin (Css=8mg/L in) has an albumin level of 2g/dl. Determine how to manage the patient. Normal levels are Css= 10-20mg/L, Css,u=1-2mg/L. A. Increase dose, since 8mg/L is below Css B. Decrease dose C. Leave dose the same C, within Css, u

Protein binding If Drug A is given with Drug B which causes a displacement of A from tissue binding sites only, therefore doubling fraction unbound in tissues. Determine what happens to the following parameters: t1/2 AUC,u AUC Vss,u Vss CL,u CL 5.2 from recitation

Protein binding When valoproic acid is given with phenytoin, phenytoin’s plasma protein binding decreases from 90% to 84%. Also, valproic acid decreases the unbound CL of phenytoin, and displaces phenytoin from tissue binding sites; no change in half-life. What happens to… AUC? AUC,u? LD? MD? 9 recitation

Hepatic cleraance

Hepatic clearance If a patient is on 600mg BID IV of Linezolid. The medical team wants to switch the patient to oral therapy. What dose should you recommend? Fe=1 600 mg BID

Hepatic clearance Calculate F* for a drug that has a ER of 0.3. Calculate F for a drug with the following characteristics: fa=0.2, fg=0.1, ER=0.3 A drug with an F* of 0.1 is classified as high or low extraction? Enzyme induction or inhibition occur almost immediately? For a drug with a ER=0.2, what is CL dependent on? A. Q B. fu C. CL,int D. B and C For a drug with a ER=0.99, what is CL dependent on? 0.7 0.014 HIGH Inhibition D A