Case Study 4
PHA 5127
Fall 2006
1 A. What happens to the bioavailability of a high extraction drug when the following
parameters are increased: Fu, QH, Clint
As Fu and Clint increase the bioavailability decreases. As QH increases the bioavailability
increases. F=QH/(Fu*Clint)
B. Explain why changes in the above parameters do not change the bioavailability of a
low extraction drug?
With a low extraction drug we know that a large amount of drug gets into the body and
avoids first pass metabolism, meaning the extraction ratio is very small. This means that
the bioavailability is about 1 (F=1-E, F~1). By changing the small extraction ratio there
is not much effect on bioavailability. Changing F from 99% from 98% is insignificant.
2. A patient with liver failure was given 70mg of a drug as an IV bolus injection. The
plasma concentrations at 3 hours and 8 hours after injection were 1.31mg/L and
0.65mg/L respectively. The drug is eliminated by hepatic metabolism and renal excretion
via glomerula filtration. The plasma protein binding for the drug is 60%... What are the
hepatic clearance and the volume of distribution of this drug in this patient? (Use
130ml/min for glomerula filtration rate).
ke =-ln(0.65/1.31)/(8-3)=0.14/hr
C0 = 1.31*exp(0.14*3)=1.99 mg/L
Vd = Dose/C0=70/1.99=35.2L
Cl = ke*Vd=0.14*35.2=4.93L/hr
Clren = GFR*fu=130*60*0.4/1000=3.12L/hr
Clhep = 4.93-3.12=1.81L/hr
3. Mark True or False
T F highly ionized substances tend to remain in the urine
T F tubular reabsorption can only be an active transport process
T F fluid is filtered across the glomerulus through passive diffusion
4. For the following situations, indicate whether the drug is filtered, reabsorbed or
actively secreted:Assume GFR is 130 mL min-1, urine flow is 1.5 ml min-1
A drug with fu = 0.1 and a ClREN = 20 mL min-1 is Actively secreted
