Pharmacokinetics

Venous equilibrium model

Venous equilibrium model Low Extraction Drug: CL= F*= High Extraction Drug: Low: CL=fup* Clint, F*=1 High: CL=Q, F*=Q/ (fup*Clint)

Venous equilibrium model If a drug has a ER=0.2 and fup is increased, describe what happens to: Css, IV: Css,u IV: Css PO: Css,u PO: Css, IV decreased Css,u IV same Css PO decreased CSs,u PO same

Venous equilibrium If a drug has a ER=0.2 and Q is increased, describe what happens to: Css, IV: Css,u IV: Css PO: Css,u PO: No effect

Venous equilibrium If a drug has a ER=0.2 and CLint is decreased, describe what happens to: Css, IV: Css,u IV: Css PO: Css,u PO: Increase ALL

Venous equilibrium If a drug has a ER=0.9 and CLint is decreased, describe what happens to: Css, IV: Css,u IV: Css PO: Css,u PO: Increases Css PO and Css,u PO. Others are the same.

Venous equilibrium If a drug has a ER=0.9 and Q is increased, describe what happens to: Css, IV: Css,u IV: Css PO: Css,u PO: Decrease both IV, Same for both PO

Venous equilibrium If a drug has a ER=0.9 and fup is increased, describe what happens to: Css, IV: Css,u IV: Css PO: Won’t ask you Css,u PO: Won’t ask you No effect for Css,IV. Increased Css,u IV

Venous equilibrium CL Vss T1/2 Low E drugs: Dec Q Inc CLint Inc fup In notes

Venous equilibrium In notes.

Venous equilibrium A patient has a yeast infection for which his physician prescribed ketoconazole. He is also taking aspirin 81 mg, simvastatin 40 mg, carvedilol 12.5 mg BID, and lisinopril 10 mg. What drug interaction is present? What happens to: Vmax Km Clint When do you expect this to happen? (Immediately or will it take time?) Simvastatin + ketoconazole No change to Vmax, Increase Km (less affinity), Decrease Clint, IMMEDIATELY!

Venous equilibrium Rifampin induces the metabolism of a substrate. What happens to: Km Vmax Clint When do you expect to see this interaction? Km no change, Vmax is increased, Clint is increased It will take some time

Pharmacokinetics Tutoring Does the dose rate need to be changed for a drug given orally with the following characteristics when it is administered with an inhibitor: CL,T=1200ml/min Fe=0.20 High E drug, Yes it does need to be changed (decreased)

Venous equilibrium TIPS: ONLY if Css,u changes would you change DR. Practice the charts in your notes! Pay attention to practice questions on recitation.