Theophylline has an average clearance of 2.8 L/hr and volume of distribution of 35 L. The therapeutic window is known to be between 10 mg/L and 20 mg/L. Theophylline can be administered as a constant rate infusion.

A drug (400 mg) is given as a multiple-dose oral treatment. The drug is completely absorbed. The clearance is 20 L/hr and the volume of distribution is 50 L. The absorption rate constant is 2.5 hr-1.

Compare the following two pharmacokinetic profiles: Case A: A hepatically cleared high-extraction drug (400 mg) is given as an oral tablet. The absorption is very rapid and approximates a bolus input.

Phenytoin is a drug with nonlinear pharmacokinetics which can be described using Michaelis-Mentin kinetics. Assume the following pharmacokinetic parameters for phenytoin after oral administration: V = 45 L, Km = 4 mg/L, Vm = 20 mg/hr, ka = 1 hr-1, F = 1

A drug that follows a two-compartment model has the following pharmacokinetic microconstants: k10 = 0.5 hr-1, k12 = 1 hr-1, k21 = 2 hr-1, V1 = 25 L.

Compare the pharmacokinetic profiles of two drugs after intravenous bolus injection and after constant rate infusion. Both drugs have a clearance of 20 L/hr, and volumes of distribution of V1 = 50 L and V2 = 100 L.

A drug that follows a two-compartment model (CL = 80 L/hr, V1 = 50 L, V2 = 200 L, k21 = 0.6 hr-1) is given orally at a dose of 400 mg in to different dosage forms. Tablet A has a rapid drug release and absorption (ka = 3 hr-1).

(1) Compare the concentration-effect relationships for two drugs with Hill factors of ?=1 and C50 values of 10 and 100 mg/L. (2) Compare the concentration-effect relationship for two drugs with the same C50 value (10 mg/L) and Hill factors of ?=1 and ?=2.

A drug (400 mg) is given as an intravenous bolus. The clearance is 10 L/hr and the volume of distribution is 50 L. Assume a one-compartment body model.

A hepatically eliminated drug (400 mg) is given as an intravenous bolus. The intrinsic clearance (CLint) is 200 L/hr. Liver blood flow is 90 L/hr, and plasma and tissue water volumes are 3 L and 39 L, respectively. Both plasma protein binding and tissue binding are 90%.

A hepatically cleared high-extraction drug (800 mg) is given as an intravenous bolus. The intrinsic clearance is 4000 L/hr and the protein binding in plasma and tissues is 80%. Assume blood and tissue water volumes of 5 and 39 L and a liver blood flow of 90 L/hr.

A drug (400 mg) is given as an oral tablet. The drug is completely absorbed. The clearance is 15 L/hr and the volume of distribution is 40 L. The absorption rate constant is 2.5 hr-1.

A hepatically cleared high-extraction drug (400 mg) is given as an oral tablet. The absorption is very rapid and approximates a bolus input. The intrinsic clearance is 5000 L/hr and the plasma protein and tissue binding are 80% and 98%, respectively. Assume blood and tissue water volumes of 5 and 39 L and a liver blood flow of 90 L/hr.

A drug with CL = 20 L/hr and V = 50 L is given orally to two different patients A and B. The dose of 400 mg is completely absorbed, however A takes the tablet with a meal (ka = 0.1 hr-1) whereas B takes it on an empty stomach (ka = 0.5 hr-1). Furthermore, A is more sensitive to the drug (C50 of 5 mg/L vs. 10 mg/L for B).

Theophylline has an average clearance of 2.8 L/hr and volume of distribution of 35 L. The therapeutic window is known to be between 10 mg/L and 20 mg/L. Immediate release oral theophylline products have a rapid absorption (ka = 3 hr-1).