Northeastern University BPPK Calculations Questions

PHS 987 Summer 2023 Assignment #4: Module #5In Vitro Drug Metabolism Assessment
An in vitro metabolism study was carried out in human liver microsomes (volume = 2 ml/mg).
The test compound is Compound A. The initial concentration was 25 uM. The reaction was
initiated and samples were collected at 5 and 10 minutes. The concentrations of Compound A in
those samples were: t = 5 min, Conc = 1.2 uM; t = 10 min, Conc = 0.055 uM.
Assume the following: MPPGL = 32, liver weight 1600 g, hepatic blood flow = 1500 ml/min, B:P
ratio = 1.5, fu,p = 0.22.
1. Calculate the in vitro intrinsic clearance of Compound A from this experiment in units of
ml/min/mgprotein.
2. Based on your answer to question 1, calculate the predicted in vivo intrinsic clearance of
Compound A in units of L/hr.
3. Assuming Compound A is 100% metabolism in vivo (fex = 0), what is the predicted clearance
of Compound A in L/hr?
4. What is the predicted hepatic extraction ratio?
5. Based on this experiment, Compound A is classified as a ________ extraction ratio compound
(fill in the blank)
6. Which of the following physiologic changes would be expected to significantly impact the
AUC of Drug A following IV bolus dosing?
a. Reduced cardiac output
b. Enzyme induction
c. Reduced plasma protein binding (assume > 50% reduction)
d. Increased bioavailability
PHS 987 Summer 2023 Assignment #4: Module #5
In Vitro Drug Metabolism Assessment
An in vitro metabolism study was carried out in human liver microsomes (volume = 2 ml/mg).
The test compound is Compound A. The initial concentration was 25 uM. The reaction was
initiated and samples were collected at 5 and 10 minutes. The concentrations of Compound A in
those samples were: t = 5 min, Conc = 1.2 uM; t = 10 min, Conc = 0.055 uM.
Assume the following: MPPGL = 32, liver weight 1600 g, hepatic blood flow = 1500 ml/min, B:P
ratio = 1.5, fu,p = 0.22.
1. Calculate the in vitro intrinsic clearance of Compound A from this experiment in units of
ml/min/mgprotein.
2. Based on your answer to question 1, calculate the predicted in vivo intrinsic clearance of
Compound A in units of L/hr.
3. Assuming Compound A is 100% metabolism in vivo (fex = 0), what is the predicted clearance
of Compound A in L/hr?
4. What is the predicted hepatic extraction ratio?
5. Based on this experiment, Compound A is classified as a ________ extraction ratio compound
(fill in the blank)
6. Which of the following physiologic changes would be expected to significantly impact the
AUC of Drug A following IV bolus dosing?
a. Reduced cardiac output
b. Enzyme induction
c. Reduced plasma protein binding (assume > 50% reduction)
d. Increased bioavailability